The present invention relates to novel sulfonamide derivatives which are useful as medicine and which inhibit activated coagulation factor X (FXa) to show anti-coagulant activity, their production and use.
For the purpose of the prevention and treatment of cardiac infarction, cerebral thrombosis, etc., it is important to inhibit formation of thrombus and various researches and developments of thrombus inhibitors such as anti-thrombin agents, platelet aggregation inhibitors, etc. have been carried out. However, anti-thrombin agents as well as platelet aggregation inhibitors have side effects such as bleeding and problems in their safety, since thrombin is a final mediator causing blood coagulation and platelet aggregation. On the other hand, FXa inhibitors specifically inhibit coagulation factor and are useful as an anti-coagulant.
So far, compounds having FXa inhibitory activity are disclosed in e.g. Japanese Unexamined Patent Publication No. 1993(H5)-208946, WO 96/16940, WO 96/40679 and WO 96/10022, etc.
However, the above compounds having FXa inhibitory activity do not have sufficient FXa inhibitory activity and, in particular, do not show sufficient action when orally administered, therefore, they are not practically useful as a medicine.
The present invention is to provide novel sulfonamide derivatives which specifically inhibit FXa, which are effective when orally administered and which are useful as a safe medicine for the prevention (prophylaxis) or treatment (therapy) of diseases caused by thrombus, ischemia or infarction.
The present inventors diligently made extensive studies and, as a result, they succeeded in synthesizing a compound or a salt thereof [hereinafter, referred to as Compound (I)], whose characteristic feature in the chemical structure lies in having (1) a divalent nitrogen-containing heterocyclic group between a sulfonyl group and a carbonyl group and (2) an amino group substituted with a hydrocarbon group, an imidoyl group or a nitrogen-containing heterocyclic group at terminals of a substituent of the carbonyl group, represented by the formula (I): 
wherein R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; the ring A is an optionally substituted divalent nitrogen-containing heterocyclic group, in addition to being substituted by the group of the formula: 
and the group of the formula: 
Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent heterocyclic group;
X is a direct bond or an optionally substituted alkylene chain; Z is (1) an amino group substituted with an optionally substituted hydrocarbon group, (2) an optionally substituted imidoyl group or (3) an optionally substituted nitrogen-containing heterocyclic group; provided that when X is a direct bond and Z is an optionally substituted 6-membered nitrogen-containing aromatic heterocyclic group, Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent unsaturated heterocyclic group; or a salt thereof, and further found that the compound (I) unexpectedly possesses potent FXa inhibitory activity based on its specific chemical structure and that the compound (I) can be safely and orally administered as a medicine for the prevention or treatment of diseases such as thrombus and infarction. Based on the finding, the present invention was accomplished.
More specifically, the present invention relates to (1) the compound (I); (2) a compound of the above (1), wherein
R1 is (1) a C1-10 alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a C3-9 cycloalkyl group, (5) a C3-6 cycloalkenyl group, (6) a C4-6 cycloalkanedienyl group, (7) a C6-14 aryl group or (8) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said groups (1)-(8) being unsubstituted or substituted by 1 to 5 substituents selected from the class consisting of
(a) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(b) a C2-6 alkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(c) a C2-6 alkynyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(d) a C6-14 aryl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e) a C3-7 cycloalkyl or C3-6 cycloalkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(f) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms, which may be substituted by C1-6 alkyl, C1-6 alkanoyl or benzoyl,
(g) an amino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl, optionally halogenated C1-6 alkoxy-carbonyl, C1-6 alkylimidoyl, formimidoyl or amidino,
(gxe2x80x2) a 3- to 8-membered cyclic amino group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(h) an imidoyl group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(i) an amidino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(j) a hydroxy group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(k) a thiol group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(l) a carboxyl group,
(lxe2x80x2) a C1-6 alkoxy-carbonyl group,
(lxe2x80x3) a C7-2 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(lxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(m) a carbamoyl group,
(mxe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(mxe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(mxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(n) a thiocarbamoyl group,
(nxe2x80x2) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(nxe2x80x3) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(nxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-thiocarbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(o) a halogen atom,
(p) a cyano group,
(q) a nitro group,
(r) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(s) a formyl group and
(sxe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C1-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms;
the ring A is a divalent 6- to 8-membered nitrogen-containing heterocyclic group which may contain, besides carbon atoms, 1 to 2 nitrogen atoms and 1 to 3 hetero-atoms selected from oxygen atom and sulfur atom, and which may be substituted, in addition to the group of the formula: 
xe2x80x83and the group of the formula: 
xe2x80x83by
(a) a hydroxy group,
(b) a halogen atom,
(c) a nitro group,
(d) a cyano group,
(e) an amino group optionally substituted with 1-2 substituents selected from
(e-1) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e-2) a carbamoyl group,
(e-2xe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(e-2xe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(e-2xe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(e-3) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(e-4) a formyl group and
(e-4xe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(f) a C1-6 alkyl group optionally substituted with halogen, amino, carboxyl or hydroxy,
(g) a C1-6 alkoxy group optionally substituted with 1 to 5 halogen atoms,
(h) a carboxyl group,
(hxe2x80x2) a C1-6 alkoxy-carbonyl group,
(hxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(hxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(i) a carbamoyl group,
(ixe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(ixe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C3-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C1-10 aralkyl or
(ixe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C1-10 aralkyl or C6-10 aryl;
Y is (1) a straight-chain C1-10 alkylene group,
(2) a straight-chain C2-6 alkenylene group,
(3) a straight-chain C2-6 alkynylene group,
(4) a C3-9 cycloalkylene group,
(5) a C3-6 cycloalkenylene group,
(6) a C4-6 cycloalkanedienylene group,
(7) a C6-10 arylene group,
(8) a C7-10 aralkylene group,
(9) a 5- to 6-membered divalent aromatic heterocyclic group containing, besides carbon atoms, 1 to 3 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom or
(10) a 5- to 6-membered divalent saturated or unsaturated non-aromatic heterocyclic group containing, besides carbon atoms, 1 to 3 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom, each of said groups (1)-(10) being unsubstituted or substituted by
(a) a hydroxy group,
(b) a halogen atom,
(c) a nitro group,
(d) a cyano group,
(e) an amino group optionally substituted with 1-2 substituents selected from
(e-1) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e-2) a carbamoyl group,
(e-2xe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(e-2xe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(e-2xe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(e-3) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(e-4) a formyl group and
(e-4xe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(f) a C1-6 alkyl group optionally substituted with halogen, amino, carboxyl or hydroxy,
(g) a C1-6 alkoxy group optionally substituted with 1 to 5 halogen atoms,
(h) a carboxyl group,
(hxe2x80x2) a C1-6 alkoxy-carbonyl group,
(hxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(hxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(i) a carbamoyl group,
(ixe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(ixe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl or
(ixe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl;
X is
(1) a direct bond or
(2) a straight-chain lower (C1-6) alkylene optionally substituted with
(a) a C1-6 alkyl group,
(b) a halogen atom,
(c) a hydroxy group,
(d) a carboxyl group,
(dxe2x80x2) a C1-6 alkoxy-carbonyl group,
(dxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms or
(dxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and
Z is
(1) an amino group substituted with 1-2 substituents selected from the class consisting of (1-1) a C1-10 alkyl group, (1-2) a C2-6 alkenyl group, (1-3) a C2-6 alkynyl group, (1-4) a C3-9 cycloalkyl group, (1-5) a C3-6 cycloalkenyl group, (1-6) a C4-6 cycloalkanedienyl group and (1-7) a C6-14 aryl group; each of said groups (1-1)-(1-7) being unsubstituted or substituted by 1 to 5 substituents selected from the class consisting of
(a) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(b) a C2-6 alkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(c) a C2-6 alkynyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(d) a C6-14 aryl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e) a C3-7 cycloalkyl or C3-6 cycloalkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(f) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms, which may be substituted by C1-6 alkyl, C1-6 alkanoyl or benzoyl,
(g) an amino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl, optionally halogenated C1-6 alkoxy-carbonyl, C1-6 alkylimidoyl, formimidoyl or amidino,
(gxe2x80x2) a 3- to 8-membered cyclic amino group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(h) an imidoyl group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(i) an amidino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(j) a hydroxy group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(k) a thiol group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(l) a carboxyl group,
(lxe2x80x2) a C1-6 alkoxy-carbonyl group,
(lxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(lxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(m) a carbamoyl group,
(mxe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(mxe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(mxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(n) a thiocarbamoyl group,
(nxe2x80x2) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(nxe2x80x3) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(nxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-thiocarbonyl group optionally having C1-6 alkyl, C1-10 aralkyl or C6-10 aryl,
(o) a halogen atom,
(p) a cyano group,
(q) a nitro group,
(r) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(s) a formyl group and
(sxe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms;
(1A) a 3- to 8-membered cyclic amino group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl, and said cyclic amino group being unsubstituted or substituted by 1 to 5 substituents selected from the class consisting of
(a) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(b) a C2-6 alkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(c) a C2-6 alkynyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(d) a C6-14 aryl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e) a C3-7 cycloalkyl or C3-6 cycloalkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(f) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms, which may be substituted by C1-6 alkyl, C1-6 alkanoyl or benzoyl,
(g) an amino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl, optionally halogenated C1-6 alkoxy-carbonyl, C1-6 alkylimidoyl, formimidoyl or amidino,
(gxe2x80x2) a 3- to 8-membered cyclic amino group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(h) an imidoyl group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(i) an amidino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(j) a hydroxy group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(k) a thiol group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(l) a carboxyl group,
(lxe2x80x2) a C1-6 alkoxy-carbonyl group,
(lxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(lxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(m) a carbamoyl group,
(mxe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(mxe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(mxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(n) a thiocarbamoyl group,
(nxe2x80x2) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(nxe2x80x3) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(nxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-thiocarbonyl group optionally having C1-6 alkyl, C7-1 aralkyl or C6-10 aryl,
(o) a halogen atom,
(p) a cyano group,
(q) a nitro group,
(r) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(s) a formyl group and
(sxe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic-group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms;
(1B) a group of the formula: xe2x80x94N(Rxe2x80x3)xe2x80x94C(Rxe2x80x2)xe2x95x90Nxe2x80x94R wherein Rxe2x80x3 is (i) a hydrogen atom or
(ii) a hydrocarbon group selected from the class consisting of a C1-10 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C3-9 cycloalkyl group, a C3-6 cycloalkenyl group, a C4-6 cycloalkanedienyl group and a C6-14 aryl group; each of said hydrocarbon groups being unsubstituted or substituted by 1 to 5 substituents selected from the class consisting of
(a) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(b) a C2-6 alkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(c) a C2-6 alkynyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(d) a C6-4 aryl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e) a C3-7 cycloalkyl or C3-6 cycloalkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(f) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms, which may be substituted by C1-6 alkyl, C1-6 alkanoyl or benzoyl,
(g) an amino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl, optionally halogenated C1-6 alkoxy-carbonyl, C1-6 alkylimidoyl, formimidoyl or amidino,
(gxe2x80x2) a 3- to 8-membered cyclic amino group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(h) an imidoyl group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(i) an amidino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(j) a hydroxy group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl, (k) a thiol group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(l) a carboxyl group,
(lxe2x80x2) a C1-6 alkoxy-carbonyl group,
(lxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(lxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(m) a carbamoyl group,
(mxe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(mxe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(mxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(n) a thiocarbamoyl group,
(nxe2x80x2) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(nxe2x80x3) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(nxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-thiocarbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(o) a halogen atom,
(p) a cyano group,
(q) a nitro group,
(r) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(s) a formyl group and
(sxe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
R is
(i) a hydrogen atom,
(ii) a hydrocarbon group selected from the class consisting of a C1-10 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C3-9 cycloalkyl group, a C3-6 cycloalkenyl group, a C4-6 cycloalkanedienyl group and a C6-14 aryl group; each of said hydrocarbon groups being unsubstituted or substituted by 1 to 5 substituents selected from the class consisting of
(a) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(b) a C2-6 alkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(c) a C2-6 alkynyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(d) a C6-14 aryl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e) a C3-7 cycloalkyl or C3-6 cycloalkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(f) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms, which may be substituted by C1-6 alkyl, C1-6 alkanoyl or benzoyl,
(g) an amino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl, optionally halogenated C1-6 alkoxy-carbonyl, C1-6 alkylimidoyl, formimidoyl or amidino,
(gxe2x80x2) a 3- to 8-membered cyclic amino group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(h) an imidoyl group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(i) an amidino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(j) a hydroxy group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(k) a thiol group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(l) a carboxyl group,
(lxe2x80x2) a C1-6 alkoxy-carbonyl group,
(lxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(lxe2x80x2xe2x80x3) a C6-1 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(m) a carbamoyl group,
(mxe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(mxe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(mxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(n) a thiocarbamoyl group,
(nxe2x80x2) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(nxe2x80x3) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C1-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C16 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(nxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-thiocarbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(o) a halogen atom,
(p) a cyano group,
(q) a nitro group,
(r) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(s) a formyl group and
(sxe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms, or
(iii) a carbonyl group having a hydrogen atom or one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms, and
Rxe2x80x2 is
(i) a hydrogen atom,
(ii) a hydrocarbon group selected from the class consisting of a C1-10 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C3-9 cycloalkyl group, a C3-6 cycloalkenyl group, a C4-6 cycloalkanedienyl group and a C6-14 aryl group; each of said hydrocarbon groups being unsubstituted or substituted by 1 to 5 substituents selected from the class consisting of
(a) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(b) a C2-6 alkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(c) a C2-6 alkynyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(d) a C6-14 aryl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e) a C3-7 cycloalkyl or C3-6 cycloalkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(f) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms, which may be substituted by C1-6 alkyl, C1-6 alkanoyl or benzoyl,
(g) an amino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl, optionally halogenated C1-6 alkoxy-carbonyl, C1-6 alkylimidoyl, formimidoyl or amidino,
(gxe2x80x2) a 3- to 8-membered cyclic amino group optionally having C1-6 alkyl, C1-10 aralkyl or C6-10 aryl,
(h) an imidoyl group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(i) an amidino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(j) a hydroxy group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(k) a thiol group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(l) a carboxyl group,
(lxe2x80x2) a C1-6 alkoxy-carbonyl group,
(lxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(lxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(m) a carbamoyl group,
(mxe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(mxe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(mxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(n) a thiocarbamoyl group,
(nxe2x80x2) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(nxe2x80x3) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C1-710 aralkyl,
(nxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-thiocarbonyl group optionally having C16 alkyl, C7-10 aralkyl or C6-10 aryl,
(o) a halogen atom,
(p) a cyano group,
(q) a nitro group,
(r) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(s) a formyl group and
(sxe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(iii) a carbonyl group having a hydrogen atom or one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5-to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(iv) an amino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl, optionally halogenated C1-6 alkoxy-carbonyl, C1-6 alkylimidoyl, formimidoyl or amidino,
(ivxe2x80x2) a 3- to 8-membered cyclic amino group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(ivxe2x80x3) an amino group substituted with 1-2 substituents selected from the class consisting of (1-1) a C1-10 alkyl group, (1-2) a C2-6 alkenyl group, (1-3) a C2-6 alkynyl group, (1-4) a C3-9 cycloalkyl group, (1-5) a C3-6 cycloalkenyl group, (1-6) a C4-6 cycloalkanedienyl group and (1-7) a C6-14 aryl group; each of said groups (1-1)-(1-7) being unsubstituted or substituted by 1 to 5 substituents selected from the class consisting of
(a) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(b) a C2-6 alkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(c) a C2-6 alkynyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(d) a C6-14 aryl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e) a C3-7 cycloalkyl or C3-6 cycloalkenyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(f) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms, which may be substituted by C1-6 alkyl, C1-6 alkanoyl or benzoyl,
(g) an amino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl, optionally halogenated C1-6 alkoxy-carbonyl, C1-6 alkylimidoyl, formimidoyl or amidino,
(gxe2x80x2) a 3- to 8-membered cyclic amino group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(h) an imidoyl group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(i) an amidino group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(j) a hydroxy group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(k) a thiol group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(l) a carboxyl group,
(lxe2x80x2) a C1-6 alkoxy-carbonyl group,
(lxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(lxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(m) a carbamoyl group,
(mxe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(mxe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(mxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(n) a thiocarbamoyl group,
(nxe2x80x2) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(nxe2x80x3) a thiocarbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(nxe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-thiocarbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(o) a halogen atom,
(p) a cyano group,
(q) a nitro group,
(r) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(s) a formyl group and
(sxe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being. unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms, or
(v) a hydroxy group optionally substituted with C1-6 alkyl group, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl;
(2) a group of the formula: xe2x80x94C(Rxe2x80x2)xe2x95x90Nxe2x80x94R wherein each symbol is as defined above; or
(3) a 5- to 6-membered aromatic or non-aromatic monocyclic nitrogen-containing heterocyclic group which contains, besides carbon atoms, 1 to 3 nitrogen atoms and optionally contains 1 to 3 hetero-atoms selected from an oxygen atom and a sulfur atom and which may be substituted by
(a) a hydroxy group,
(b) a halogen atom,
(c) a nitro group,
(d) a cyano group,
(e) an amino group optionally substituted with 1-2 substituents selected from
(e-1) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano group or amidino,
(e-2) a carbamoyl group,
(e-2xe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(e-2xe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C7-10 aralkyl,
(e-2xe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl,
(e-3) a sulfonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(e-4) a formyl group and
(e-4xe2x80x2) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(f) a C1-6 alkyl group optionally substituted with halogen, amino, carboxyl or hydroxy,
(g) a C1-6 alkoxy group optionally substituted with 1 to 5 halogen atoms,
(h) a carboxyl group,
(hxe2x80x2) a C1-6 alkoxy-carbonyl group,
(hxe2x80x3) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(hxe2x80x2xe2x80x3) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(i) a carbamoyl group,
(ixe2x80x2) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(ixe2x80x3) a carbamoyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-10 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said alkyl, cycloalkyl, aryl, aralkyl and heterocyclic groups being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms; and having another substituent selected from C1-6 alkyl, C3-6 cycloalkyl and C1-2 aralkyl or
(ixe2x80x2xe2x80x3) a 3- to 8-membered cyclic amino-carbonyl group optionally having C1-6 alkyl, C7-10 aralkyl or C6-10 aryl;
(3) a compound of the above (1), wherein R1 is an optionally substituted hydrocarbon group;
(4) a compound of the above (1), wherein R1 is an aryl group optionally substituted with a halogen atom;
(5) a compound of the above (1), wherein the ring A is a group of the formula: 
xe2x80x83wherein B is CH or a nitrogen atom, and m and n are respectively 2 or 3;
(6) a compound of the above (5), wherein B is a nitrogen atom;
(7) a compound of the above (5), wherein m and n are 2;
(8) a compound of the above (1), wherein Y is an optionally substituted divalent aromatic heterocyclic group;
(9) a compound of the above (1), wherein Y is an optionally substituted phenylene group;
(10) a compound of the above (1), wherein Y is an optionally substituted cyclohexylene group;
(11) a compound of the above (1), wherein Z is an optionally substituted nitrogen-containing heterocyclic group;
(12) a compound of the above (1), wherein Z is an optionally substituted amidino group;
(13) a compound of the above (1), wherein Z is an optionally substituted guanidino group;
(14) a compound of the above (1), wherein
Z is (1) a mono- or di-C1-6 alkylamino group which may be further substituted with phenyl at the alkyl moiety, (2) guanidino, (3) formimidoyl-amino, (4) acetimidoylamino or (5) piperidino;
(15) a compound of the above (1), wherein
Z is a group of the formula: xe2x80x94N(Rxe2x80x3)xe2x80x94C(Rxe2x80x2)xe2x95x90Nxe2x80x94R or a group of the formula: xe2x80x94C(Rxe2x80x2)xe2x95x90Nxe2x80x94R wherein
Rxe2x80x3 is a hydrogen atom or a C1-6 alkyl group,
R is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkanoyl group or a benzoyl group,
Rxe2x80x2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkanoyl group, a benzoyl group, an amino group optionally substituted with 1-2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, or a C1-6 alkoxy group;
(16) a compound of the above (1), wherein
Z is a group of the formula: xe2x80x94NHxe2x80x94C(Rxe2x80x2)xe2x95x90NH or a group of the formula: xe2x80x94C(Rxe2x80x2)xe2x95x90NH wherein
Rxe2x80x2 is a C1-6 alkyl group or an amino group optionally substituted with 1-2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl;
(17) a compound of the above (1), wherein
R1 is (1) a C1-10 alkyl group, (2) a C2-6 alkenyl group, (3) a C2-6 alkynyl group, (4) a C6-14 aryl group or (5) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; each of said groups (1)-(5) being unsubstituted or substituted by
(a) a C1-6 alkyl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano or amidino,
(b) a C6-14 aryl group optionally substituted with C1-6 alkoxy, halogen, C1-6 alkyl, amino, hydroxy, cyano or amidino,
(c) a heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms, which may be substituted by C1-6 alkyl, C1-6 alkanoyl or benzoyl,
(d) an amino group optionally substituted with C1-6 alkyl, C1-6 alkanoyl, benzoyl, optionally halogenated C1-6 alkoxy-carbonyl, C1-6 alkylimidoyl, formimidoyl or amidino,
(e) an imidoyl group optionally substituted with C1-6 alkyl, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(f) an amidino group optionally substituted with C1-6 alkyl, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(g) a hydroxy group optionally substituted with C1-6 alkyl, C1-6 alkanoyl, benzoyl or optionally halogenated C1-6 alkoxy-carbonyl,
(h) a carboxyl group,
(i) a C1-6 alkoxy-carbonyl group,
(j) a C1-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(k) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms,
(l) a halogen atom,
(m) a cyano group,
(n) a nitro group or
(o) a carbonyl group having one substituent selected from C1-6 alkyl, C3-6 cycloalkyl, C6-10 aryl, C7-11 aralkyl and heterocyclic group selected from the class consisting of (i) a 5- to 6-membered aromatic monocyclic heterocyclic group, (ii) a 8- to 12-membered aromatic fused heterocyclic group and (iii) a 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and containing 1 to 4 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom besides carbon atoms; the ring A is a group of the formula: 
xe2x80x83wherein B is CH or a nitrogen atom, and m and n are respectively 2 or 3, said group being unsubstituted or substituted, in addition to the group of the formula: 
xe2x80x83and the group of the formula: 
xe2x80x83by
(a) a carboxyl group,
(b) a C1-6 alkoxy-carbonyl group,
(c) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms or
(d) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms;
Y is (1) a straight-chain C1-10 alkylene group,
(2) a C3-9 cycloalkylene group,
(3) a C6-10 arylene group,
(4) a C7-10 aralkylene group,
(5) a 5- to 6-membered divalent aromatic heterocyclic group containing, besides carbon atoms, 1 to 3 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom or
(6) a 5- to 6-membered divalent saturated or unsaturated non-aromatic heterocyclic group containing, besides carbon atoms, 1 to 3 hetero-atoms selected from oxygen atom, sulfur atom and nitrogen atom, each of said groups (1)-(6) being unsubstituted or substituted by
(a) a halogen atom,
(b) a cyano group,
(c) a C1-6 alkyl group optionally substituted with halogen, amino, carboxyl or hydroxy or
(d) a C1-6 alkoxy group optionally substituted with 1 to 5 halogen atoms;
X is a direct bond or a straight-chain C1-6 alkylene; and
Z is (1) an amino group substituted with 1-2 substituents selected from the class consisting of (1-1) a C1-10 alkyl group and (1-2) a C6-14 aryl group;
(2) a group of the formula: xe2x80x94N(Rxe2x80x3)xe2x80x94C(Rxe2x80x2)xe2x95x90Nxe2x80x94R or a group of the formula: xe2x80x94C(Rxe2x80x2)xe2x95x90Nxe2x80x94R wherein
Rxe2x80x3 is a hydrogen atom or a C1-6 alkyl group,
R is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkanoyl group or a benzoyl group, and
Rxe2x80x2 is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkanoyl group, a benzoyl group or an amino group optionally substituted with 1-2 substituents selected from C1-6 alkyl, C1-6 alkanoyl or benzoyl, or a C1-6 alkoxy group; or
(3) a 5- to 6-membered aromatic or non-aromatic monocyclic nitrogen-containing heterocyclic group which contains, besides carbon atoms, 1 to 3 nitrogen atoms and optionally contains 1 to 3 hetero-atoms selected from an oxygen atom and a sulfur atom and which may be substituted by
(a) a halogen atom,
(b) an amino group,
(c) a C1-6 alkyl group optionally substituted with halogen, amino, carboxyl or hydroxy,
(d) a carboxyl group,
(e) a C1-6 alkoxy-carbonyl group,
(f) a C7-12 aryloxycarbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms or
(g) a C6-10 aryl-C1-4 alkoxy-carbonyl group being unsubstituted or substituted by hydroxy, amino optionally having 1 to 2 substituents selected from C1-6 alkyl, C1-6 alkanoyl and benzoyl, halogen, nitro, cyano, C1-6 alkyl optionally substituted with 1 to 5 halogen atoms or C1-6 alkoxy optionally substituted with 1 to 5 halogen atoms;
(18) a compound of the above (1), which is 1-(6-chloronaphthalene-2-sulfonyl)-4-[4-(4-pyridyl)benzoyl]piperazine, 1-(6-chloronaphthalene-2-sulfonyl)-4-[4-(1H-imidazol-1-yl)benzoyl]piperazine, 1-(6-chloronaphthalene-2-sulfonyl)-4-[2-(4-pyridyl)-4-methyl-5-thiazolylcarbonyl]piperazine, 1-(trans-4-acetimidoylaminocyclohexan-1-ylcarbonyl)-4-(6-chloronaphthalene-2-sulfonyl)piperazine, 1-(6-chloronaphthalene-2-sulfonyl)-4-(trans-4-guanidinocyclohexan-1-ylcarbonyl)piperazine, or a salt thereof;
(19) a pharmaceutical composition comprising a compound of the above (1) or a salt thereof;
(20) a composition of the above (19) which is an anti-coagulant;
(21) a composition of the above (19) which is an inhibitor of activated coagulation factor X;
(22) a composition of the above (19) which is for the prevention or treatment of deep vein thrombosis, cardiac infarction or cerebral thrombosis;
(23) use of a compound or a salt thereof of the above (1) for manufacturing a pharmaceutical composition;
(24) use of a compound or a salt thereof of the above (1) for manufacturing an anti-coagulant;
(25) use of a compound or a salt thereof of the above (1) for manufacturing a pharmaceutical composition for inhibiting activated coagulation factor X;
(26) use of a compound or a salt thereof of the above (1) for manufacturing a pharmaceutical composition for treating or preventing deep vein thrombosis, cardiac infarction or cerebral thrombosis;
(27) a method for inhibiting activated coagulation factor X in a mammal which comprises administering an effective amount of a compound or a salt thereof of the above (1);
(28) a method for preventing or treating deep vein thrombosis, cardiac infarction or cerebral thrombosis in a mammal which comprises administering an effective amount of a compound or a salt thereof of the above (1) to said mammal;
(29) a method for producing a compound of the above (1) or a salt thereof, which comprises reacting a compound of the formula: R1SO2Q wherein Q is a halogen atom and the other symbol is as defined in the above (1), or a salt thereof with a compound of the formula: 
xe2x80x83wherein the ring A is an optionally substituted divalent nitrogen-containing heterocyclic group, in addition to being substituted by the group represented by the formula: 
xe2x80x83and the other symbols are as defined in the above (1), or a salt thereof; or reacting a compound of the formula: 
xe2x80x83wherein the ring A is an optionally substituted divalent nitrogen-containing heterocyclic group, in addition to being substituted by the group represented by the formula: 
xe2x80x83and the other symbols are as defined in the above (1), or a salt thereof with a compound of the formula:
Zxe2x80x94Xxe2x80x94Yxe2x80x94COOH
xe2x80x83wherein each symbol is as defined in the above (1), or a salt thereof, or its reactive derivatives;
(30) a method for producing a compound of the formula: 
xe2x80x83wherein R10 is a lower alkyl group and the other symbols are as defined in the above (1), or a salt thereof, which comprises reacting a compound of the formula: 
xe2x80x83wherein each symbol is as defined above, or a salt thereof with a compound of the formula: R10OH wherein R10 is as defined above, or a salt thereof;
(31) a method for producing a compound of the formula: 
xe2x80x83wherein R11 and R12 are independently a hydrogen atom or an optionally substituted hydrocarbon group and the other symbols are as defined in the above (1), or a salt thereof, which comprises reacting a compound of the formula: 
xe2x80x83wherein each symbol is as defined in the above (29), or a salt thereof with a compound of the formula: 
xe2x80x83wherein each symbol is as defined above, or a salt thereof;
(32) a method for producing a compound of the formula: 
xe2x80x83wherein the ring B is an optionally substituted divalent non-aromatic heterocyclic group, R14 is a hydrogen atom or an optionally substituted hydrocarbon group, V is a hydrogen atom, an optionally substituted hydrocarbon group or an amino group which may be substituted with an optionally substituted hydrocarbon group and the other symbols are as defined in the above (1), or a salt thereof, which comprises reacting a compound of the formula: 
xe2x80x83wherein each symbol is as defined above, or a salt thereof with a compound of the formula: 
xe2x80x83wherein R15 is a lower alkyl group, U is an oxygen atom or an sulfur atom and the other symbols are as defined above, or a salt thereof;
(33) a method for producing a compound of the formula: 
xe2x80x83wherein R13 is a hydrogen atom or an optionally substituted hydrocarbon group, R14 is a hydrogen atom or an optionally substituted hydrocarbon group, V is a hydrogen atom, an optionally substituted hydrocarbon group or an amino group which may be substituted with an optionally substituted hydrocarbon group and the other symbols are as defined in the above (1), or a salt thereof, which comprises reacting a compound of the formula: 
xe2x80x83wherein each symbol is as defined above, or a salt thereof with a compound of the formula: 
xe2x80x83wherein R15 is a lower alkyl group, U is an oxygen atom or an sulfur atom, the other symbols are as defined above, or a salt thereof; etc.
In the above formula, R1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group (preferably, an optionally substituted hydrocarbon group).
Examples of hydrocarbon groups in the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1 include e.g. an aliphatic hydrocarbon group, an alicyclic hydrocarbon group and an aryl group, etc. Among others, an aryl group, etc. is preferable.
Examples of the xe2x80x9caliphatic hydrocarbon groupxe2x80x9d exemplified by the hydrocarbon group include e.g. a straight-chain or branched aliphatic hydrocarbon group such as an alkyl group, an alkenyl group, an alkynyl group, etc.
Examples of the alkyl group include e.g. C1-10 alkyl group (preferably C1-6 alkyl, etc.), etc. such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, 1-methylpropyl, n-hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 3,3-dimethylpropyl, 2-ethylbutyl, n-heptyl, 1-methylheptyl, 1-ethylhexyl, n-octyl, 1-methyl-heptyl, nonyl, etc.
Examples of the alkenyl group include e.g. C2-6 alkenyl group, etc. such as vinyl, allyl, isopropenyl, 2-methylallyl, 1-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-ethyl-1-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, etc.
Examples of the alkynyl group include e.g. C2-6 alkynyl group such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, etc.
Examples of the xe2x80x9calicyclic hydrocarbon groupxe2x80x9d exemplified by the hydrocarbon group include e.g. a saturated or unsaturated alicyclic hydrocarbon group such as a cycloalkyl group, a cycloalkenyl group, a cycloalkanedienyl group, etc.
Examples of the xe2x80x9ccycloalkyl groupxe2x80x9d include e.g. C3-9 cycloalkyl, etc. such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, etc.
Examples of the xe2x80x9ccycloalkenyl groupxe2x80x9d include e.g. C3-6 cycloalkenyl group, etc. such as 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-cyclohexen-1-yl, 1-cyclobuten-1-yl, 1-cyclopenten-1-yl, etc.
Examples of the xe2x80x9ccycloalkanedienyl groupxe2x80x9d include e.g. C4-6 cycloalkanedienyl group, etc. such as 2,4-cyclopentadien-1-yl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl, etc.
Examples of the xe2x80x9caryl groupxe2x80x9d exemplified by the hydrocarbon group include e.g. a monocyclic or fused aromatic hydrocarbon group. Among others, C6-14 aryl group, etc. such as phenyl, naphthyl, anthryl, phenathryl, acenaphthyl, etc. is preferable. In particular, phenyl, 1-naphthyl, 2-naphthyl, etc. are preferable.
Examples of the heterocyclic group in the xe2x80x9coptionally substituted heterocyclic groupxe2x80x9d represented by R1 include e.g. an aromatic heterocyclic group, saturated or unsaturated non-aromatic heterocyclic group (alicyclic heterocyclic group) etc., which contains, besides carbon atoms, at least one hetero-atom (preferably 1 to 4 hetero-atoms, more preferably 1 to 2 hetero-atoms) consisting of 1 to 3 kinds of hetero-atoms (preferably 1 to 2 kinds of hetero-atoms) selected from oxygen atom, sulfur atom, nitrogen atom, etc.
Examples of the xe2x80x9caromatic heterocyclic groupxe2x80x9d include an aromatic monocyclic heterocyclic group such as 5- to 6-membered aromatic monocyclic heterocyclic group, etc. (e.g. furyl, thienyl, pyrrolyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc.); an aromatic fused heterocyclic group such as 8- to 12-membered aromatic fused heterocyclic group (preferably, heterocyclic group consisting of the above-mentioned 5- or 6-membered aromatic monocyclic heterocyclic group fused with a benzene ring or heterocyclic group consisting of the above-mentioned 5- or 6-membered aromatic monocyclic heterocyclic group fused with the same or different above-mentioned 5- or 6-membered aromatic monocyclic heterocyclic group), etc. (e.g. benzofuranyl, isobenzofuranyl, benzothienyl, indolyl, isoindolyl, 1H-indazolyl, benzindazolyl, benzoxazolyl, 1,2-benzoisooxazolyl, benzothiazolyl, benzopyranyl, 1,2-benzoisothiazolyl, 1H-benzotriazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, purinyl, pteridinyl, carbazolyl, xcex1-carbolinyl, xcex2-carbolinyl, xcex3-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxathinyl, thianthrenyl, phenanthridinyl, phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl, etc.); etc.
Examples of the xe2x80x9cnon-aromatic heterocyclic groupxe2x80x9d include a 3- to 8-membered (preferably 5- or 6-membered) saturated or unsaturated (preferably saturated) non-aromatic heterocyclic group (alicyclic heterocyclic group), etc. such as oxiranyl, azetidinyl, oxetanyl, thiethanyl, pyrrolidinyl, tetrahydrofuryl, thiolanyl, piperidyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, piperazinyl, etc.
Examples of the substituent of the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d and xe2x80x9coptionally substituted heterocyclic groupxe2x80x9d represented by R1 include an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group, an optionally substituted aryl group, an optionally substituted cycloalkyl or cycloalkenyl group, an optionally substituted heterocyclic group, an optionally substituted amino group, an optionally substituted imidoyl group, an optionally substituted amidino group, an optionally substituted hydroxyl group, an optionally substituted thiol group, an optionally esterified carboxyl group, an optionally substituted carbamoyl group, an optionally substituted thiocarbamoyl group, a halogen atom (e.g. fluorine, chlorine, bromine, iodine, etc., preferably chlorine, bromine, etc.), a cyano group, a nitro group, an acyl group derived from a sulfonic acid, an acyl group derived from an carboxylic acid, etc.
The xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d and xe2x80x9coptionally substituted heterocyclic groupxe2x80x9d may have 1 to 5 substituents as described above (preferably 1 to 3 substituents) at any possible position.
Examples of the aryl group in the xe2x80x9coptionally substituted aryl groupxe2x80x9d as the substituent include C6-14 aryl group, etc. such as phenyl, naphthyl, anthryl, phenathryl, acenaphthyl, etc. Said aryl groups may have 1 or 2 substituents at any possible positions. Examples of the substituent include a lower alkoxy group (e.g. C1-6 alkoxy group, etc. such as methoxy, ethoxy, propoxy, etc.), a halogen atom (e.g. fluorine, chlorine, bromine, iodine, etc.), a lower alkyl group (e.g. C1-6 alkyl group, etc. such as methyl, ethyl, propyl, etc.), an amino group, a hydroxy group, a cyano group, an amidino group, etc.
Examples of the cycloalkyl group in the xe2x80x9coptionally substituted cycloalkyl groupxe2x80x9d as the substituent include C3-7 cycloalkyl group, etc. such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc. Said cycloalkyl groups may have the same kind and number of substituents as those of the above described xe2x80x9coptionally substituted aryl.
Examples of the cycloalkenyl group in the xe2x80x9coptionally substituted cycloalkenyl groupxe2x80x9d as the substituent include e.g. C3-6 cycloalkenyl group, etc. such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, etc. Said cycloalkenyl groups may have the same kind and number of substituents as those of the above described xe2x80x9coptionally substituted aryl.
Examples of the alkyl group in the xe2x80x9coptionally substituted alkyl groupxe2x80x9d as the substituent include e.g. C1-6 alkyl etc. such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, 1-methylpropyl, n-hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 3,3-dimethylpropyl, etc. Said alkyl groups may have the same kind and number of substituents as those of the above described xe2x80x9coptionally substituted aryl.
Examples of the alkenyl group in the xe2x80x9coptionally substituted alkenyl groupxe2x80x9d as the substituent include e.g. C2-6 alkenyl group, etc. such as vinyl, allyl, isopropenyl, 2-methylallyl, 1-propenyl, 2-methyl-i-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-ethyl-1-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, etc. Said alkenyl groups may have the same kind and number of substituents as those of the above described xe2x80x9coptionally substituted aryl.
Examples of the alkynyl group in the xe2x80x9coptionally substituted alkynyl groupxe2x80x9d as the substituent include e.g. C2-6 alkynyl group, etc. such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, etc. Said alkynyl groups may have the same kind and number of substituents as those of the above described xe2x80x9coptionally substituted aryl.
Examples of the heterocyclic group in the xe2x80x9coptionally substituted heterocyclic groupxe2x80x9d as the substituent include e.g. an aromatic heterocyclic group, saturated or unsaturated non-aromatic heterocyclic group (alicyclic heterocyclic group) etc., which contains, besides carbon atoms, at least one hetero-atom (preferably 1 to 4 hetero-atoms, more preferably 1 to 2 hetero-atoms) consisting of 1 to 3 kinds of hetero-atoms (preferably 1 to 2 kinds of hetero-atoms) selected from oxygen atom, sulfur atom, nitrogen atom, etc.
Examples of the xe2x80x9caromatic heterocyclic groupxe2x80x9d include an aromatic monocyclic heterocyclic group such as a 5- to 6-membered aromatic monocyclic heterocyclic group, etc. (e.g. furyl, thienyl, pyrrolyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc.); an aromatic fused heterocyclic group such as 8- to 12-membered aromatic fused heterocyclic group (preferably, heterocyclic group consisting of the above-mentioned 5- or 6-membered aromatic monocyclic heterocyclic group fused with a benzene ring or heterocyclic group consisting of the above-mentioned 5- or 6-membered aromatic monocyclic heterocyclic group fused with the same or different above-mentioned 5- or 6-membered aromatic monocyclic heterocyclic group), etc. (e.g. benzofuranyl, isobenzofuranyl, benzothienyl, indolyl, isoindolyl, 1H-indazolyl, benzindazolyl, benzoxazolyl, 1,2-benzoisooxazolyl, benzothiazolyl, benzopyranyl, 1,2-benzoisothiazolyl, 1H-benzotriazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, purinyl, pteridinyl, carbazolyl, xcex1-carbolinyl, xcex2-carbolinyl, xcex3-carbolinyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl, phenoxathinyl, thianthrenyl, phenanthridinyl, phenanthrolinyl, indolizinyl, pyrrolo[1,2-b]pyridazinyl, pyrazolo[1,5-a]pyridyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, 1,2,4-triazolo[4,3-a]pyridyl, 1,2,4-triazolo[4,3-b]pyridazinyl, etc.); etc.
Examples of the xe2x80x9cnon-aromatic heterocyclic groupxe2x80x9d include a 3- to 8-membered (preferably 5- or 6-membered) saturated or unsaturated (preferably saturated) non-aromatic heterocyclic group (alicyclic heterocyclic group), etc. such as oxiranyl, azetidinyl, oxetanyl, thiethanyl, pyrrolidinyl, tetrahydrofuryl, thiolanyl, piperidyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, piperazinyl, etc.
Examples of the substituent of the xe2x80x9coptionally substituted heterocyclic groupxe2x80x9d as the substituent include a lower alkyl group (e.g. C1-6 alkyl group, etc. such as methyl, ethyl, propyl, etc.), an acyl group (e.g. C1-6 alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc., benzoyl, etc.), etc.
Examples of the substituent in the xe2x80x9coptionally substituted amino groupxe2x80x9d, xe2x80x9coptionally substituted imidoyl groupxe2x80x9d, xe2x80x9coptionally substituted amidino groupxe2x80x9d, xe2x80x9coptionally substituted hydroxy groupxe2x80x9d and xe2x80x9coptionally substituted thiol groupxe2x80x9d as the substituent include e.g. a lower alkyl group (e.g. C1-6 alkyl group, etc. such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc.), an acyl group such as C1-6 alkanoyl (e.g. formyl, acetyl, propionyl, pivaloyl, etc.), benzoyl, etc., an optionally halogenated C1-6 alkoxy-carbonyl (e.g. trifluoromethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl, trichloromethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, etc.), etc. In addition, the xe2x80x9camino groupxe2x80x9d in the xe2x80x9coptionally substituted amino groupxe2x80x9d as the substituent may be substituted with an optionally substituted imidoyl group (e.g., C1-6 alkylimidoyl, formimidoyl, amidino, etc.), etc. and two substituents of the xe2x80x9camino groupxe2x80x9d may form a cyclic amino group together with a nitrogen atom. Examples of said cyclic amino group include e.g. 3- to 8-membered (preferably 5- to 6-membered) cyclic amino group, etc. such as 1-azetidinyl, 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl and 1-piperazinyl which may have at the 4-position a lower alkyl group (e.g. C1-6 alkyl group, etc. such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, etc.), an aralkyl group (e.g. C7-10 aralkyl group, etc. such as benzyl, phenethyl, etc.), an aryl group (e.g. C6-10 aryl group, etc. such as phenyl, 1-naphthyl, 2-naphthyl, etc.), etc.
Examples of the xe2x80x9coptionally substituted carbamoyl groupxe2x80x9d include unsubstituted carbamoyl, N-mono-substituted carbamoyl group and N,N-di-substituted carbamoyl group.
The xe2x80x9cN-mono-substituted carbamoyl groupxe2x80x9d is a carbamoyl group having one substituent on the nitrogen atom and said substituent include e.g. a lower alkyl group (e.g. C1-6 alkyl group, etc. such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc,), a cycloalkyl group (e.g. C3-6 cycloalkyl group, etc. such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), an aryl group (e.g. C610 aryl group, etc. such as phenyl, 1-naphthyl, 2-naphthyl, etc.), an aralkyl group (e.g. C7-10 aralkyl group, preferably phenyl-C1-4 alkyl group, etc. such as benzyl, phenethyl, etc.), a heterocyclic group (e.g. the above described xe2x80x9cheterocyclic groupxe2x80x9d as the substituent of the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1, etc.), etc. Said lower alkyl group, cycloalkyl group, aryl group, aralkyl group and heterocyclic group may have a substituent and examples of the substituent include e.g. a hydroxy group, an optionally substituted amino group [said amino group may have 1 to 2 substituents (e.g. a lower alkyl group (e.g. C1-6 alkyl group, etc. such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc.), an acyl group (e.g. C1-6 alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc., benzoyl, etc.), etc.)], a halogen atom (e.g. fluorine, chlorine, bromine, iodine, etc.), a nitro group, a cyano group, a lower alkyl group optionally substituted with 1 to 5 halogen atoms (e.g. fluorine, chlorine, bromine, iodine, etc.), a lower alkoxy group optionally substituted with 1 to 5 halogen atoms (e.g. fluorine, chlorine, bromine, iodine, etc.), etc. Said lower alkyl group include e.g. C1-6 alkyl group, etc. such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, etc. and in particular methyl, ethyl, etc. are preferable. Said lower alkoxy group include e.g. C,6 alkoxy group, etc. such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc. and in particular methoxy, ethoxy, etc. are preferable. These substituents may be same or different and the above described lower alkyl group, cycloalkyl group, aryl group, aralkyl group and heterocyclic group may have 1 or 2 to 3 (preferably 1 or 2) substituents.
The xe2x80x9cN,N-di-substituted carbamoyl groupxe2x80x9d is a carbamoyl group having two substituents on the nitrogen atom. Examples of one of the substituents include the same as those of the above described xe2x80x9cN-mono-substituted carbamoyl groupxe2x80x9d and examples of the other substituent include e.g. a lower alkyl group (e.g. C1-6 alkyl group, etc. such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, etc.), C3-6 cycloalkyl group (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), C7-10 aralkyl group (e.g. benzyl, phenethyl, etc., preferably phenyl-C1-4 alkyl group, etc.), etc. In addition, two substituents of the xe2x80x9cN,N-di-substituted carbamoyl groupxe2x80x9d may form a cyclic amino-carbamoyl group together with a nitrogen atom. Examples of said cyclic amino-carbamoyl group include e.g. 3- to 8-membered (preferably 5- to 6-membered) cyclic amino-carbamoyl group, etc. such as 1-azetidinylcarbonyl, 1-pyrrolidinylcarbonyl, piperidinocarbonyl, morpholinocarbonyl, 1-piperazinylcarbonyl and 1-piperazinylcarbonyl which may have at the 4-position a lower alkyl group (e.g. C1-6 alkyl group, etc. such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, etc.), an aralkyl group (e.g. C7-10 aralkyl group, etc. such as benzyl, phenethyl, etc.), an aryl group (e.g. C6-10 aryl group, etc. such as phenyl, 1-naphthyl, 2-naphthyl, etc.), etc.
Examples of the substituent in the xe2x80x9coptionally substituted thiocarbamoyl groupxe2x80x9d include the same substituent as those in the above described xe2x80x9coptionally substituted carbamoyl groupxe2x80x9d.
Examples of the xe2x80x9coptionally esterified carboxyl groupxe2x80x9d in the present specification include a carboxyl group as well as a lower alkoxycarbonyl group, an aryloxycarbonyl group, aralkyloxycarbonyl group, etc.
Examples of the xe2x80x9clower alkoxycarbonyl groupxe2x80x9d include e.g. C1-6 alkoxy-carbonyl group, etc. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, isopentyloxycarbonyl, neopentyloxycarbonyl, etc. Among others, C1-3 alkoxy-carbonyl group, etc. such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc. are preferable.
Examples of the xe2x80x9caryloxycarbonyl groupxe2x80x9d include e.g. C7-10 aryloxy-carbonyl group, etc. such as phenoxycarbonyl, 1-naphthoxycarbonyl, 2-naphthoxycarbonyl, etc.
Examples of the xe2x80x9caralkyloxycarbonyl groupxe2x80x9d include e.g. C7-10 aralkyloxy-carbonyl group, etc. (preferably, C6-10 aryl-C1-4 alkoxy-carbonyl, etc.) such as benzyloxycarbonyl, phenethyloxycarbonyl, etc.
Said xe2x80x9caryloxycarbonyl groupxe2x80x9d and xe2x80x9caralkyloxycarbonyl groupxe2x80x9d may have a substituent. Examples of the substituent include the same kind and number of the substituents of the aryl group and aralkyl group as the substituent for the above described N-mono-substituted carbamoyl group.
Examples of the xe2x80x9cacyl group derived from a sulfonic acidxe2x80x9d as the substituent include a sulfonyl group having one substituent which the above described xe2x80x9cN-mono-substituted carbamoyl groupxe2x80x9d have on the nitrogen atom, etc., preferably, C1-6 alkyl sulfonyl, etc. such as methanesulfonyl, ethane-sulfonyl, etc.
Examples of the xe2x80x9cacyl group derived from a carboxylic acidxe2x80x9d as the substituent include a carbonyl group having a hydrogen atom or one substituent which the above described xe2x80x9cN-mono-substituted carbamoyl groupxe2x80x9d have on the nitrogen atom, etc., preferably, C1-6 alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc. benzoyl, etc.
In the above formula, the ring A represents an optionally substituted divalent nitrogen-containing heterocyclic group, in addition to the group of the formula: 
and the group of the formula: 
Examples of the xe2x80x9cdivalent nitrogen-containing heterocyclic groupxe2x80x9d in the xe2x80x9coptionally substituted divalent nitrogen-containing heterocyclic groupxe2x80x9d represented by the ring A include a divalent 6- to 8-membered nitrogen-containing heterocyclic group which may contain, besides carbon atoms, at least one nitrogen atom (preferably 1 to 2 nitrogen atoms) and 1 to 3 hetero-atoms selected from oxygen atom, sulfur atom, etc.
Examples of the xe2x80x9cdivalent 6- to 8-membered nitrogen-containing heterocyclic groupxe2x80x9d include e.g. a divalent 6-membered nitrogen-containing heterocyclic group which contains 1 to 2 nitrogen atoms such as piperidinediyl (piperidine-1,2-, 1,3- or 1,4-diyl), piperazinediyl (piperazine-1,2-, 1,3- or 1,4-diyl), molpholinediyl (molpholine-2,4- or 3,4-diyl), thiomolpholinediyl (thiomolpholine-2,4- or 3,4-diyl), etc.; a divalent 7-membered nitrogen-containing heterocyclic group which contains 1 to 2 nitrogen atoms such as homopiperidinediyl (homopiperidine-1,2-, 1,3- or 1,4-diyl), homopiperazinediyl (piperazine-1,2-, 1,3-, 1,4-, 1,5-, 1,6- or 1,7-diyl), etc.; a divalent 8-membered nitrogen-containing heterocyclic group which contains 1 to 2 nitrogen atoms such as 1,4-diazacyclooctanediyl (1,4-diazacyclooctane-1,2-, 1,3-, 1,4-, 1,5-, 1,6-, 1,7- or 1,8-diyl), 1,5-diazacyclooctanediyl (1,5-diazacyclooctane-1,2-, 1,3-, 1,4- or 1,5-diyl) etc.; etc.
Examples of the substituents of the xe2x80x9cdivalent nitrogen-containing heterocyclic groupxe2x80x9d include e.g. a hydroxy group, a halogen atom (e.g. fluorine, chlorine, bromine, iodine, etc.), a nitro group, a cyano group, an optionally substituted amino group, an optionally substituted lower alkyl group, a lower alkoxy group optionally substituted with 1 to 5 halogen atoms (e.g. fluorine, chlorine, bromine, iodine, etc.), an optionally esterified carboxyl group, an optionally substituted carbamoyl group, etc. Said xe2x80x9cdivalent nitrogen-containing heterocyclic groupxe2x80x9d may have 1 to 3 (preferably 1 to 2) of these substituents at any possible position.
Examples of the substituents of the xe2x80x9coptionally substituted amino groupxe2x80x9d include 1-2 substituents selected from an optionally substituted alkyl group, an optionally substituted carbamoyl group, an acyl group derived from a sulfonic acid, an acyl group derived from a carboxylic acid, etc. Examples of said xe2x80x9coptionally substituted alkyl groupxe2x80x9d, xe2x80x9coptionally substituted carbamoyl groupxe2x80x9d, xe2x80x9can acyl group derived from a sulfonic acidxe2x80x9d and xe2x80x9can acyl group derived from a carboxylic acidxe2x80x9d include the xe2x80x9coptionally substituted alkyl groupxe2x80x9d, xe2x80x9coptionally substituted carbamoyl groupxe2x80x9d, xe2x80x9can acyl group derived from a sulfonic acidxe2x80x9d and xe2x80x9can acyl group derived from a carboxylic acidxe2x80x9d as exemplified by the substituents for the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1.
Preferable examples of the xe2x80x9coptionally substituted amino groupxe2x80x9d include an amino group optionally substituted by 1-2 substituents selected from (1) a lower (C1-6) alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc., (2) mono- or di-lower (C1-6) alkyl carbamoyl group, (3) C1-6 alkyl sulfonyl such as methanesulfonyl, ethanesulfonyl, etc., (4) C1-6 alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc. and (5) benzoyl.
Examples of the xe2x80x9clower alkyl groupxe2x80x9d in the xe2x80x9cthe optionally substituted a lower alkyl groupxe2x80x9d include e.g. C1-6alkyl group, etc. such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc., and in particular methyl, ethyl, etc. are preferable.
Examples of the substituents for the xe2x80x9clower alkyl groupxe2x80x9d include e.g. a halogen atom (e.g. fluorine, chlorine, bromine, iodine, etc.), an amino group, a carboxyl group, hydroxy group, etc. Said xe2x80x9clower alkyl groupxe2x80x9d may have 1 to 5 (preferably 1 or 2) substituents at any possible position.
Examples of the xe2x80x9clower alkoxy groupxe2x80x9d in the xe2x80x9clower alkoxy group optionally substituted with 1 to 5 halogen atomsxe2x80x9d include e.g. C1-6 alkoxy group, etc. such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, etc. and in particular methoxy, ethoxy, etc. are preferable.
Examples of the xe2x80x9coptionally esterified carboxyl groupxe2x80x9d include the optionally esterified carboxyl group as exemplified by the substituents for the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1.
Examples of the xe2x80x9coptionally substituted carbamoyl groupxe2x80x9d include the optionally substituted carbamoyl group as exemplified by the substituents for the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1.
As the ring A, a group of the formula: 
wherein B is CH or a nitrogen atom, and m and n are 2 or 3 is preferable.
In the above formula, B is CH or a nitrogen atom and a nitrogen atom is preferable, as B.
In the above formula, m and n are 2 or 3, and preferably m and n are 2.
In particular, the ring A is preferably piperazinediyl (more preferably piperazine-1,4-diyl).
In the above formula, Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent heterocyclic group (preferably divalent hydrocarbon group or divalent unsaturated heterocyclic group, and more preferably, divalent hydrocarbon group or divalent aromatic heterocyclic group).
Among others, Y is preferably an optionally substituted divalent hydrocarbon group or an optionally divalent unsaturated heterocyclic group, and more preferably an optionally substituted divalent hydrocarbon group or an optionally divalent aromatic heterocyclic group. In particular, Y is preferably an optionally substituted phenylene group, an optionally substituted cyclohexylene group or an optionally substituted divalent aromatic heterocyclic group.
Examples of the xe2x80x9cdivalent hydrocarbon groupxe2x80x9d in the xe2x80x9coptionally substituted divalent hydrocarbon groupxe2x80x9d represented by Y include a saturated or unsaturated, straight-chain or cyclic divalent hydrocarbon group (preferably, a saturated straight-chain divalent hydrocarbon group, a saturated cyclic divalent hydrocarbon group or a unsaturated cyclic divalent hydrocarbon group, more preferably, a saturated straight-chain divalent hydrocarbon group, a saturated cyclic divalent hydrocarbon group or an divalent aromatic hydrocarbon group, etc.).
Examples of the saturated straight-chain divalent hydrocarbon group include a straight-chain C1-6 alkylene (preferably, a straight-chain C1-4 alkylene, etc. such as methylene, ethylene, etc.), etc. such as methylene, ethylene, propylene, butylene, pentylene, etc. which is a divalent group formed by removing a terminal hydrogen atom from a straight-chain alkyl group (e.g. C1-10 alkyl group (preferably C1-6 alkyl, more preferably C1-4 alkyl, etc.), etc. such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, etc.
Examples of the unsaturated straight-chain divalent hydrocarbon group include a straight-chain C2-6 alkenylene, C2-6 alkynylene, etc. which is a divalent group formed by removing a terminal hydrogen atom from a straight-chain alkenyl group (e.g. C2-6 alkenyl group, etc. such as vinyl, allyl, 1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, etc.), a straight-chain alkynyl group (e.g. C2-6 alkynyl group, etc. such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexyntl, 2-hexyntl, 3-hexyntl, 4-hexyntl, 5-hexyntl, etc.), etc.
Examples of the saturated cyclic divalent hydrocarbon group include a divalent group formed by removing a hydrogen atom at an optional position (preferably a hydrogen atom on a carbon atom which is different from the carbon atom at the 1-position, more preferably a hydrogen atom on a carbon atom which is farthest from the carbon atom at the 1-position) from a cycloalkyl group (e.g. C3-9 cycloalkyl (preferably C5-7 cycloalkyl, more preferably cyclohexyl, etc.), etc. such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, etc.). Preferable examples of the saturated cyclic divalent hydrocarbon group include C5-7 cycloalkylene (more preferably 1,4-cyclohexylene, etc.). etc.
Examples of the unsaturated cyclic divalent hydrocarbon group include a divalent group formed by removing a hydrogen atom at an optional position (preferably a hydrogen atom on a carbon atom which is different from the carbon atom at the 1-position, more preferably a hydrogen atom on a carbon atom which is farthest from the carbon atom at the 1-position) from a cycloalkenyl group (e.g. C3-6 cycloalkenyl group, etc. such as 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1-yl, 3-cyclohexen-1-yl, 1-cyclobuten-1-yl, 1-cyclopenten-1-yl, etc.), a cycloalkanedienyl group (e.g. C4-6 cycloalkanedienyl group, etc. such as 2,4-cycloalkanedien-1-yl, 2,4-cyclohexadien-1-yl, 2,5-cyclohexadien-1-yl, etc.), an aryl group (e.g. C6-10 aryl group, etc. such as phenyl, naphthyl, etc., preferably phenyl), an aralkylyl group (e.g. C7-10 aralkyl group, etc. such as benzyl, phenethyl, etc., preferably benzyl), etc. Among others, phenylene is preferable and in particular 1,4-phenylene is preferable.
Examples of the substituents for the xe2x80x9coptionally substituted divalent hydrocarbon groupxe2x80x9d represented by Y include the same substituents as those of the above described xe2x80x9cdivalent nitrogen-containing heterocyclic groupxe2x80x9d represented by the ring A.
Examples of the xe2x80x9cdivalent heterocyclic groupxe2x80x9d in the xe2x80x9coptionally substituted divalent heterocyclic groupxe2x80x9d represented by Y include a 5- to 6-membered divalent aromatic heterocyclic group, a 5- to 6-membered divalent saturated or unsaturated non-aromatic heterocyclic group (alicyclic heterocyclic group), etc., which contains, besides carbon atoms, at least one hetero-atom (preferably 1 to 3 hetero-atoms, more preferably 1 to 2 hetero-atoms) consisting of 1 to 3 kinds of hetero-atoms (preferably 1 to 2 kinds of hetero-atoms) selected from oxygen atom, sulfur atom, nitrogen atom, etc.
Examples of the xe2x80x9cdivalent aromatic heterocyclic groupxe2x80x9d include a divalent group formed by removing two hydrogen atoms at different positions from a 5-membered heterocyclic ring such as furan, thiophene, pyrrole, oxazole, isooxazole, thiazole, isothiazole, imidazole, pyrazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,3-triazole, 1,2,4-triazole, etc., a 6-membered heterocyclic ring such as pyridine, pyridazine, pyrimidine, 1,2,4-triazine, 1,3,5-triazine, etc.
Examples of the xe2x80x9cdivalent non-aromatic heterocyclic groupxe2x80x9d include a 5- to 6-membered saturated or unsaturated (preferably saturated) non-aromatic heterocyclic group (alicyclic heterocyclic group), etc. such as pyrrolidine, tetrahydrofuran, piperidine, tetrahydropyran, molpholine, thiomolpholine, piperazine, etc.
Examples of the substituents for the xe2x80x9coptionally substituted divalent heterocyclic groupxe2x80x9d represented by Y include the same substituents as those of the above described xe2x80x9cdivalent nitrogen-containing heterocyclic groupxe2x80x9d represented by the ring A.
Among others, Y is preferably an optionally substituted divalent aromatic group.
In the above formula, Z is an amino group substituted with an optionally substituted hydrocarbon group, an optionally substituted imidoyl group or an optionally substituted nitrogen-containing heterocyclic group, and said amino group, imidoyl group or nitrogen-containing heterocyclic group binds to the group Y through xe2x80x9ca direct bond or an optionally substituted alkylene chainxe2x80x9d represented by X.
Examples of the xe2x80x9calkylene chainxe2x80x9d in the xe2x80x9coptionally substituted alkylene chainxe2x80x9d represented by X include a straight-chain lower (C1-6) alkylene, etc. such as methylene, ethylene, propylene, butylene, pentylene, etc. Among others, C1-4 alkylene, etc. such as methylene, ethylene, etc. is preferable.
Examples of the substituents for the xe2x80x9calkylene chainxe2x80x9d include a lower alkyl group (e.g. C1-6 alkyl, etc. such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc.), a halogen atom (e.g. fluorine, chlorine, bromine, iodine, etc.), hydroxy group, an optionally esterified carboxyl group (the same xe2x80x9coptionally esterified carboxyl groupxe2x80x9d as exemplified by the substituents for the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1), etc. Said xe2x80x9calkylene chainxe2x80x9d may have 1 to 3 of these substituents at any possible position.
Examples of the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d in the xe2x80x9camino group substituted with (one or two) optionally substituted hydrocarbon groupxe2x80x9d are similar to the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1. In addition, two of the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d may be combined to form a cyclic amino together with a nitrogen atom. Examples of said cyclic amino group include a 3- to 8-membered (preferably 5- to 6-membered) cyclic amino such as 1-azetidinyl, 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl optionally having a lower alkyl group (e.g. C1-6 alkyl group, etc. such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl, etc.), an aralkyl group (e.g. C7-10 aralkyl group, etc. such as benzyl, phenethyl, etc.), an aryl group (e.g. C6-10 aryl group, etc. such as phenyl, 1-naphthyl, 2-naphthyl, etc.), etc. at the 4-position., etc. Said cyclic amino group may have the same kind and number of the substituents as exemplified by those for the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1.
In addition, when the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d as the substituent in the xe2x80x9camino group substituted with an optionally substituted hydrocarbon groupxe2x80x9d is substituted by an optionally substituted imidoyl group, the xe2x80x9camino group substituted with an optionally substituted hydrocarbon groupxe2x80x9d represented by Z represents an amino group substituted with an optionally substituted imidoyl group shown below represented by Z. Examples of said amino group substituted with an optionally substituted imidoyl group include a group of the formula:
xe2x80x94N(Rxe2x80x3)xe2x80x94C(Rxe2x80x2)xe2x95x90Nxe2x80x94R
wherein Rxe2x80x3 is a hydrogen atom or an optionally substituted hydrocarbon group, R is a hydrogen atom, an optionally substituted hydrocarbon group or an acyl group derived from a carboxylic acid and, Rxe2x80x2 is a hydrogen atom, an optionally substituted hydrocarbon group, an acyl group derived from a carboxylic acid, an optionally substituted amino group or an optionally substituted hydroxy group.
In the above formula, examples of xe2x80x9can optionally substituted hydrocarbon groupxe2x80x9d represented by R, Rxe2x80x2 and Rxe2x80x3 include the same xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d as the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1. Examples of the xe2x80x9cacyl group derived from a carboxylic acidxe2x80x9d represented by R and Rxe2x80x2 include the same xe2x80x9cacyl group derived from a carboxylic acidxe2x80x9d as the substituent for the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1. Examples of the xe2x80x9coptionally substituted hydroxy groupxe2x80x9d represented by Rxe2x80x2 include the same xe2x80x9coptionally substituted hydroxy groupxe2x80x9d as the substituent for the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1. Examples of the xe2x80x9coptionally substituted amino groupxe2x80x9d represented by Rxe2x80x2 include the same xe2x80x9coptionally substituted amino groupxe2x80x9d as the substituent for the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1 or an amino group optionally having 1-2 of the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1.
The compound (I) wherein R is an acyl group derived from a carboxylic acid is useful for a pro-drug of the compound (I) wherein R is an hydrogen atom.
Examples of the xe2x80x9cacyl group derived from a carboxylic acidxe2x80x9d represented by R include the same xe2x80x9cacyl group derived from a carboxylic acidxe2x80x9d as the substituent for the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1. In addition, the xe2x80x9cacyl group derived from a carboxylic acidxe2x80x9d represented by R may be an optionally esterified carboxyl group such as a group of the formula: xe2x80x94COORxe2x80x2xe2x80x3 wherein Rxe2x80x2xe2x80x3 is an optionally substituted hydrocarbon group. Examples of the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by Rxe2x80x2xe2x80x3 include the same xe2x80x9c optionally substituted hydrocarbon groupxe2x80x9d represented by R1. Preferred examples of the xe2x80x9chydrocarbon groupxe2x80x9d in the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by Rxe2x80x2xe2x80x3 include C1-6alkyl, C2-6 alkenyl, C3-6 cycloalkyl, C6-10 aryl, C6-10 aryl-C1-4 alkyl, etc. Each of them may have the same kind and number of the substituents as exemplified by those for the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1. Among others, as the group of the formula: xe2x80x94COORxe2x80x2xe2x80x3, C1-6 alkoxy-carbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, etc.), C1-6 alkanoyloxy-C1-6 alkoxy-carbonyl (e.g. pivaloyloxymethoxycarbonyl, 1-(acetoxy)-ethoxycarbonyl, acetoxy-tert-butoxycarbonyl, etc.), C1-6 alkoxy-carbonyloxy-C1-6 alkoxy-carbonyl (e.g. ethoxycarbonyloxymethoxycarbonyl, etc.), 5-C1-4 alkyl-2-oxo-dioxolen-4-yl-C1-6 alkoxy-carbonyl (e.g. 5-methyl-2-oxo-dioxolen-4-ylmethoxycarbonyl, etc.), etc. are preferable.
Specific examples of the xe2x80x9camino group substituted with an optionally substituted hydrocarbon groupxe2x80x9d include a mono- or di-lower (C1-6) alkyl amino group which may be further substituted with an aryl group (preferably, phenyl), etc. (e.g. methylamino, ethylamino, benzylmethylamino, dimethylamino, diethylamino, diisobutylamino, diisopropylamino, N-ethyl-t-butylamino, benzylmethylamino, etc.), a guanidino group, a formimidoylamino group, an acetimidoylamino group, piperidino group, etc.
Specific examples of the xe2x80x9coptionally substituted imidoyl groupxe2x80x9d include a group of the formula: xe2x80x94C(Rxe2x80x2)xe2x95x90Nxe2x80x94R wherein each symbol is as defined above.
In the above formula, Rxe2x80x3 is preferably a hydrogen atom or a lower alkyl group (e.g. C1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc.), R is preferably a hydrogen atom, a lower alkyl group (e.g. C1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc.), or an acyl group (e.g. C1-6 alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc., benzoyl, etc.), and Rxe2x80x2 is preferably a hydrogen atom, a lower alkyl group (e.g. C1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc.), an acyl group (e.g. C1-6 alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc., benzoyl, etc.), an optionally substituted amino group (e.g. an amino group optionally substituted with same or different substituents selected from a lower alkyl group (e.g. C1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc.) and an acyl group (e.g. C1-6 alkanoyl such as formyl, acetyl, propionyl, pivaloyl, etc., benzoyl, etc.)), or a lower alkoxy group (e.g. C1-6 alkoxy group such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, etc.).
In the above formula, as Rxe2x80x3 and R, a hydrogen atom or a lower alkyl group is preferable. Among others, a hydrogen atom is preferable.
In the above formula, as Rxe2x80x2, a hydrogen atom, a lower alkyl group or an optionally substituted amino group is preferable. Among others, a lower alkyl group or an optionally substituted amino group is preferable and, in particular, an optionally substituted amino group (preferably, amino optionally substituted with C1-4alkyl, etc.) is preferable.
Examples of the xe2x80x9cnitrogen-containing heterocyclic groupxe2x80x9d in the xe2x80x9coptionally substituted nitrogen-containing heterocyclic groupxe2x80x9d include an aromatic nitrogen-containing heterocyclic group and a saturated or unsaturated non-aromatic nitrogen-containing heterocyclic group (alicyclic heterocyclic group), which contains, besides carbon atoms, at least one nitrogen atom (preferably 1 to 3 nitrogen atoms) and optionally contains 1 to 3 hetero-atoms selected from a oxygen atom, a sulfur atom, etc.
Examples of the xe2x80x9caromatic nitrogen-containing heterocyclic groupxe2x80x9d include aromatic monocyclic nitrogen-containing heterocyclic group, its N-oxide, etc. such as pyrrolyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, imidazolyl (1H-imidazol-1-yl, 1H-imidazol-4-yl, etc.), pyrazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, furazanyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl (1,2,4-triazolyl-1-yl, 1,2,4-triazolyl-4-yl, etc.), tetrazolyl, pyridyl (2-, 3- or 4-pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, etc. Among others, 5- to 6-membered aromatic monocyclic nitrogen-containing heterocyclic groups are preferable.
Examples of the xe2x80x9cnon-aromatic nitrogen-containing heterocyclic groupxe2x80x9d include azetidinyl, pyrrolidinyl, piperidyl (2-, 3- or 4-piperidyl), morpholinyl, thiomorpholinyl, piperazinyl (1-piperazinyl, etc.), homopiperazinyl, etc. Among others, 5- to 6-membered non-aromatic monocyclic nitrogen-containing heterocyclic groups are preferable.
Examples of the substituents of the xe2x80x9cnitrogen-containing heterocyclic groupxe2x80x9d represented by Z include the same substituents as those of the above described xe2x80x9cdivalent nitrogen-containing heterocyclic groupxe2x80x9d represented by the ring A.
Z is preferably an optionally substituted nitrogen-containing heterocyclic group, etc. and an optionally substituted aromatic nitrogen-containing heterocyclic group, etc. is more preferable, provided that when X is a direct bond and Z is an optionally substituted 6-membered nitrogen-containing heterocyclic group, Y is preferably an optionally substituted divalent hydrocarbon group or an optionally substituted divalent unsaturated heterocyclic group.
Preferable combinations of Y and Z include
(1) Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent heterocyclic group, and Z is an amino group substituted with an optionally substituted hydrocarbon group, an optionally substituted imidoyl group, an optionally substituted 5-membered aromatic nitrogen-containing heterocyclic group or an optionally substituted non-aromatic nitrogen-containing heterocyclic group (preferably an amino group substituted with hydrocarbon group, an optionally substituted imidoyl group or an optionally substituted non-aromatic nitrogen-containing heterocyclic group, more preferably an amino group substituted with a hydrocarbon group or an optionally substituted imidoyl group);
(2) Z is an amino group substituted with an optionally substituted hydrocarbon group, an optionally substituted imidoyl group or an optionally substituted nitrogen-containing heterocyclic group, and Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent unsaturated heterocyclic group (preferably an optionally substituted divalent hydrocarbon group or an optionally substituted divalent aromatic heterocyclic group, more preferably an optionally substituted, an optionally substituted phenylene group or an optionally substituted divalent aromatic heterocyclic group);
(3) Z is an optionally substituted 6-membered nitrogen-containing heterocyclic group, and Y is an optionally substituted, divalent hydrocarbon group or an optionally substituted divalent unsaturated heterocyclic group (preferably an optionally substituted divalent hydrocarbon group or an optionally substituted divalent aromatic heterocyclic group, more preferably an optionally substituted, phenylene group or an optionally substituted divalent aromatic heterocyclic group);
(4) Y is a divalent saturated heterocyclic group, Z is an amino group substituted with an optionally substituted hydrocarbon group, an optionally substituted imidoyl group, an optionally substituted 5-membered aromatic nitrogen-containing heterocyclic group or an optionally substituted non-aromatic nitrogen-containing heterocyclic group (preferably an amino group substituted with a hydrocarbon group, an optionally substituted imidoyl group or an optionally substituted non-aromatic nitrogen-containing heterocyclic group, more preferably an amino group substituted with a hydrocarbon group or an optionally substituted imidoyl group);
(5) Z is an amino group substituted with an optionally substituted hydrocarbon group, an optionally substituted imidoyl group, an optionally substituted 5-membered aromatic nitrogen-containing heterocyclic group or an optionally substituted non-aromatic nitrogen-containing heterocyclic group (preferably an amino group substituted with a hydrocarbon group, an optionally substituted imidoyl group or an optionally substituted non-aromatic nitrogen-containing heterocyclic group, more preferably an amino group substituted with a hydrocarbon group or an optionally substituted imidoyl group), and Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent unsaturated heterocyclic group (preferably an optionally substituted divalent hydrocarbon group or an optionally substituted divalent aromatic heterocyclic group, more preferably an optionally substituted phenylene group or an optionally substituted divalent aromatic heterocyclic group); etc.
Examples of the salts of the compound (I) include a pharmaceutically acceptable salt, etc. such as an acid addition salt (e.g. a salt with acetic acid, lactic acid, succinic acid, maleic acid, tartaric acid, citric acid, gluconic acid, ascorbic acid, benzoic acid, methanesulfonic acid, p-toluenesulfonic acid, cinnamic acid, fumaric acid, phosphoric acid, hydrochloric acid, nitric acid, hydrobromic acid, hydriodic atom acid, sulfamic acid, sulfuric acid, etc.), a metal salt (e.g. a salt with sodium, potassium, magnesium, calcium, etc.), an organic base (e.g. trimethylamine, triethylamine, pyridine, picoline, N-methylpyrrolidine, N-methylpiperidine, N-methylmolpholine, etc.), etc.
The compounds (I) of this invention can be produced by, for example, methods as described below or those similar to the methods described below.
Each compound described in the following reaction schemes may be in the form of a salt, unless it inhibits the reaction and examples of the salts are the same as those of the compound (I).
Method A
A compound (II) or a salt thereof represented by the formula:
R1SO2Qxe2x80x83xe2x80x83(II)
wherein Q is a halogen atom, and the other symbols are as defined above is reacted with a compound (III) or a salt thereof represented by the formula: 
wherein each symbol is as defined above to produce the compound (I).
In the formula (II), Q is a halogen atom. Examples of the halogen atom represented by Q include fluorine, chlorine, bromine, iodine, etc.
This production method is carried out by reacting a compound (II) or a salt thereof with a compound (III) or a salt thereof. Examples of the salt of the compound (II) or (III) include an acid addition salt with an acid which can form an acid addition salt with the above described compound (I).
This production method is usually carried out in a solvent. Any solvent can be used unless it inhibits this production method.
Examples of the solvent include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, etc., ethers such as dioxane, tetrahydrofuran, diethylether, tert-butylmethylether, diisopropylether, ethyleneglycol-dimethylether, etc., esters such as ethyl formate, ethyl acetate, n-butyl acetate, etc., halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, 1,2-dichloroethane etc., hydrocarbons such as n-hexane, benzene, toluene, etc., amides such as formamide, N,N-dimethylformamide,-N,N-dimethylacetamide, etc., ketones such as acetone, methylethylketone, methylisobutylketone, etc., nitrites such as acetonitrile, propionitrile, etc., etc., and additionally dimethylsulfoxide, sulfolane (tetramethylenesulfone), hexamethylphosphorylamide, water, etc., and these can be used singly or as a mixture.
If necessary, this production method can be carried out in the presence of a base. Examples of the base include an inorganic base such as lithium hydroxide, potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, etc., a tertiary amine such as triethylamine, tri(n-propyl)amine, tri(n-butyl)amine, diisopropylethylamine, cyclohexyldimethylamine, pyridine, lutidine, xcex3-collidine, N,N-dimethylaniline, N-methylpiperidine, N-methylpyrrolidine, N-methylmolpholine, etc.
In the reaction, about 1 to about 5 moles (preferably about 1 to about 3 moles) of the compound (II) is used per 1 mole of compound (III).
The reaction temperature ranges from about xe2x88x9280xc2x0 C. to about 100xc2x0 C., preferably about xe2x88x9250xc2x0 C. to about 80xc2x0 C.
The reaction time varies depending on kind of the compound (II) or (III), kind of the solvent, the reaction temperature, etc. and usually ranges from about 1 minute to about 72 hours, preferably about 15 minutes to about 24 hours.
Method B
A compound (IV) or a salt thereof represented by the formula: 
wherein each symbol is as defined above is reacted with a compound (V) or a salt thereof or its reactive derivatives represented by the formula:
Zxe2x80x94Xxe2x80x94Yxe2x80x94COOHxe2x80x83xe2x80x83(V)
wherein each symbol is as defined above to produce a compound (I) or a salt thereof.
This production method is carried out by reacting a compound (IV) or a salt thereof with a free acid(V) or a salt thereof (iorganic salt, organic salt, etc.) or its reactive derivatives (e.g. acid halide, acid azide, acid anhydride, mixed acid anhydride, active amide, active ester, active thioester, etc.). Examples of the salt of the compound (IV) include an acid addition salt with an acid which can form an acid addition salt with the above described compound (I).
Examples of the in organic salt of the compound (V) include a salt with alkali metal (e.g. a salt with sodium, potassium, etc.), a salt with alkaline earth metal (e.g. a salt with calcium, etc.), etc. Examples of the organic salt of the compound (V) include a salt with trimethylamine, triethylamine, tert-butyldimethylamine, dibenzylmethylamine, benzyl-dimethylamine, N,N-dimethylaniline, pyridine, quinoline, etc.
Examples of the acid halide include acid chloride, acid bromide, etc. Examples of the mixed acid anhydride include mono-C1-4alkyl carbonate mixed acid anhydride (e.g. a mixed acid anhydride of a free acid (V) with monomethylcarbonate, monoethylcarbonate, monoisopropylcarbonate, monoisobutylcarbonate, mono-(tert-butyl)carbonate, mono-benzylcarbonate, mono(p-nitrobenzyl)carbonate, monoallylcarbonate, etc.), C1-6 alicyclic carboxylic acid mixed acid anhydride (e.g. a mixed acid anhydride of a free acid (V) with acetic acid, cyanoacetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, pivalic acid, trifluoroacetic acid, trichloroacetic acid, acetoacetic acid, etc.), C7-11 aromatic carboxylic acid mixed acid anhydride (e.g. a mixed acid anhydride of a free acid (V) with benzoic acid, p-toluic acid, p-chlorobenzoic acid, etc.), organic sulfonic acid mixed acid anhydride (e.g. a mixed acid anhydride with methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc.), etc. Examples of the active amide include an amide with nitrogen-containing heterocyclic compound (e.g. an acid amide of a free acid (V) with pyrazole, imidazole, benzotriazole, etc.; Said nitrogen-containing heterocyclic compound is optionally substituted with C1-6 alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, etc.), C1-6 alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, etc.), a halogen atom (e.g. fluorine, chlorine, bromine, etc.), oxo, thioxo, C1-6 alkylthio (e.g. methylthio, ethylthio, propylthio, butylthio, etc.), etc.), etc.
Examples of the active ester include organic phosphoric acid ester (e.g. diethoxyphosphoric acid ester, diphenoxyphosphoric acid ester, etc.), p-nitrophenylester, 2,4-dinitrophenylester, cyanomethylester, pentachlorophenylester, N-hydroxysuccinimide ester, N-hydroxy-phthalimide ester, 1-hydroxybenzotriazole ester, 6-chloro-1-hydroxy-benzotriazole ester, 1-hydroxy-1H-2-pyridone ester, etc.
Examples of the active thioester include ester with aromatic heterocyclic thiol compound (e.g. 2-pyridylthiol ester, 2-benzo-thiazolylthiol ester), etc., said heterocyclic group being optionally substituted with C1-6alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, etc.), C1-6 alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, etc.), a halogen atom (e.g. fluorine, chlorine, bromine, etc.), C1-6 alkyl thio (e.g. methylthio, ethylthio, propylthio, butylthio, etc.), etc.
This production method is usually carried out in a solvent and, if necessary, in the presence of a base or a condensing agent (e.g. carbodiimides (e.g. DCC, WSC, DIC, etc.), phosphoric acid derivatives (e.g. cyanophosphorate diethyl, DPPA, BOP-Cl, etc.), etc.).
Examples of the solvent and the base are the same as those described in the above Method A.
In the reaction, about 1 to about 5 moles (preferably about 1 to about 2 moles) of the compound (V) is used per 1 mole of the compound (IV).
The reaction temperature ranges about xe2x88x9250xc2x0 C. to about 150xc2x0 C., preferably about xe2x88x9220xc2x0 C. to about 100xc2x0 C.
The reaction time varies from depending on kind of the compound (IV) or (V), kind of the solvent and. the base, the reaction temperature, etc. and usually ranges from about 1 minute to about 100 hours, preferably about 15 minutes to about 48 hours.
Method C 
wherein T is a halogen atom or xe2x80x94Oxe2x80x94SO2R4 (R4 is a lower alkyl group optionally substituted with a halogen atom or a phenyl group which may be substituted, and the other symbols are as defined above.
In the above formula (VI), examples of the halogen atom represented by T include fluorine, chlorine, bromine, iodine, etc.
In the above formula, examples of the lower alkyl group represented by R4 include a C1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethyl-butyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, etc. Among others, a C1-4 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc. is preferable.
Examples of the lower alkyl group substituted with a halogen atom (e.g. fluorine, chlorine, bromine, iodine, etc.) represented by R4 include trichloromethyl, trifluoromethyl, etc.
Examples of the substituents for the phenyl group represented by R4 include a lower alkyl group (the same as the above described lower alkyl group represented by R4), a lower alkoxy group (e.g. C1-6 alkoxy group such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, etc.), a halogen atom (e.g. fluorine, chlorine, bromine, iodine, etc.), a nitro group, a cyano group, a carboxyl group, etc.
This production method is carried out by reacting the compound (VI) with the compound (VII). The-reaction is usually carried out in a solvent. Any solvent can be used unless it inhibits this production method.
Examples of the solvent include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, etc., ethers such as dioxane, tetrahydrofuran, diethylether, tert-butylmethylether, diisopropylether, ethyleneglycol-dimethylether, etc., esters such as ethyl formate, ethyl acetate, n-butyl acetate, etc., halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, 1,2-dichloroethane, etc., hydrocarbons such as n-hexane, benzene, toluene, etc., amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, etc., ketones such as acetone, methylethylketone, methylisobutylketone, etc., nitrites such as acetonitrile, propionitrile, etc., etc., and additionally dimethylsulfoxide, sulforane, hexamethylphosphorylamide, water, etc., and these can be used singly or as a mixture.
If necessary, this production method can be carried out , in the presence of a base. Examples of the base include an alkali metal hydride such as potassium hydride, sodium hydride, etc., a metal C1-6 alkoxide such as lithium ethoxide, lithium tert-butoxide, sodium methoxide, sodium ethoxide, sodium tert-butoxide, etc., an inorganic base such as lithium hydroxide, potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, etc., a tertiary amine such as triethylamine, tri(n-propyl)amine, tri(n-butyl) amine, diisopropylethylamine, cyclohexyldimethylamine, pyridine, lutidine, xcex3-collidine, N,N-dimethylaniline, N-methylpiperidine, N-methylpyrrolidine, N-methylmolpholine, etc.
In the reaction, about 1 to about 100 moles (preferably about 1 to about 50 moles) of the compound (VII) is used per 1 mole of compound (VI).
The reaction temperature ranges from about xe2x88x9230xc2x0 C. to about 250xc2x0 C., preferably about xe2x88x9210 to about 200xc2x0 C.
The reaction time varies depending on kind of the compound (VI) or (VII), kind of the solvent, the reaction temperature, etc. and usually ranges from about 1 minute to about 72 hours, preferably about 15 minutes to about 24 hours.
Method D
A compound (D-I) or a salt thereof represented by the formula: 
wherein each symbol is as defined above is reacted with a compound (D-II) represented by the formula: R10OH wherein R10 is a lower alkyl group to produce a compound (D-III) or a salt thereof represented by the formula: 
wherein each symbol is as defined above.
In the above formula, examples of the lower alkyl represented by R10 include a C1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, etc. Among others, a C1-4 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc. is preferable.
This production method is carried out by reacting the compound (D-I) with the compound (D-II) to produce the compound (D-III). The reaction is usually carried out in a solvent. The compound (D-II) can be used as the solvent and any solvent can be used unless it inhibits this production method.
Examples of the solvent include ethers such as dioxane, tetrahydrofuran, diethylether, tert-butylmethylether, diisopropylether, dimethoxyethane, ethyleneglycol-dimethylether, etc., esters such as ethyl formate, ethyl acetate, n-butyl acetate, etc., halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, 1,2-dichloroethane, etc., hydrocarbons such as n-hexane, benzene, toluene, etc., amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, etc., ketones such as acetone, methylethylketone, methylisobutylketone, etc., nitriles such as acetonitrile, propionitrile, etc., etc., and additionally dimethylsulfoxide, sulforane, hexamethylphosphorylamide, water, etc., and these can be used singly or as a mixture.
This production method is usually carried out in the presence of acid or base catalyst. Examples of the acid catalyst include an inorganic acid such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, etc., an organic acid such as methanesulfonic acid, ethanesulfonic acid, camphorsulfonic acid, benzenesulfonic acid, toluenesulfonic acid, etc. Among others, halogenated hydride such as hydrochloric acid, hydrobromic acid, etc. is preferable. Examples of base catalyst include metal alkoxide of a compound (D-II). Preferable examples of the metal include alkali metal such as sodium, potassium, lithium, etc.
The reaction is carried out by using about 1 to about 10000 moles (preferably about 1 to about 1000 moles) of the compound (D-II) per 1 mole of the compound (D-I). Amount of the catalyst to be employed ranges from about 0.001 mole to an over excess amount.
The reaction temperature ranges from about xe2x88x9250xc2x0 C. to about 150xc2x0 C., preferably xe2x88x9230xc2x0 C. to about 100xc2x0 C.
The reaction time varies depending on kind of the compound (D-I) or (D-II), kind of the solvent, the reaction temperature, etc. and usually ranges from about 1 minute to about 96 hours, preferably about 30 minutes to about 48 hours.
The compound (D-III) is reacted with a compound (D-IV) or a salt thereof represented by the formula: 
wherein R11 and R12 are independently a hydrogen atom or an optionally substituted hydrocarbon group to produce a compound (D-V) or a salt thereof represented by the formula: 
wherein each symbol is as defined above.
This production method is carried out by reacting the compound (D-III) and the compound (D-IV). The reaction is usually carried out in a solvent. Any solvent can be used unless it inhibits this production method.
Examples of the solvent include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, etc., ethers such as dioxane, tetrahydrofuran, diethylether, tert-butylmethylether, diisopropylether, .ethylenpeglycol-dimethylether, etc., esters such as ethyl formate, ethyl acetate, n-butyl acetate, etc., halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, 1,2-dichloroethane etc., hydrocarbons such as n-hexane, benzene, toluene, etc., amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, etc., ketones such as acetone, methylethylketone, methylisobutylketone, etc., nitrites such as acetonitrile, propionitrile, etc., etc., and additionally dimethylsulfoxide, sulfolane (tetramethylenesulfone), hexamethylphosphorylamide, water, etc., and these can be used singly or as a mixture.
In the reaction, about 1 mole or more (usually over excess amount) of the compound (D-IV) is used per 1 mole of the compound (D-III).
The reaction temperature ranges from about xe2x88x9250xc2x0 C. to about 150xc2x0 C., preferably about xe2x88x9230xc2x0 C. to about 100xc2x0 C.
The reaction time varies depending on kind of the compound (D-III) or (D-IV), kind of the solvent, the reaction temperature, etc. and usually ranges from about 15 minutes to about 120 hours, preferably about 30 minutes to about 96 hours.
Method E
A compound (E-I) or a salt thereof represented by the formula: 
wherein the ring B is an optionally substituted divalent non-aromatic heterocyclic group, and the other symbols are as defined above is reacted with a compound (E-III) or a salt thereof represented by the formula: 
wherein R14 is a hydrogen atom or an optionally substituted hydrocarbon group, R15 is a lower alkyl group, U is an oxygen atom or an sulfur atom, V is a hydrogen atom, an optionally substituted hydrocarbon group or an amino group optionally having an optionally substituted hydrocarbon group to produce a compound (E-IV) or a salt thereof represented by the formula: 
wherein each symbol is as defined above.
In addition, a compound (E-II) or a salt thereof represented by the formula: 
wherein R13 is a hydrogen atom or an optionally substituted hydrocarbon group, and the other symbols are as defined above is reacted with a compound (E-II) or a salt thereof to produce a compound (E-V) or a salt thereof represented by the formula: 
wherein each symbol is as defined above.
In the above formulas (E-I) to (E-V), examples of the xe2x80x9coptionally substituted divalent non-aromatic heterocyclic groupxe2x80x9d represented by the ring B include the same optionally substituted divalent non-aromatic heterocyclic group as exemplified by the above described xe2x80x9coptionally substituted divalent heterocyclic groupxe2x80x9d represented by Y. As the non-aromatic heterocyclic, a 5- to 8-membered (preferably 5- to 6-membered) ring is preferable and a saturated heterocyclic ring is more preferable. Examples of the xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R13, R14 and V include the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1. Examples of the xe2x80x9clower alkyl groupxe2x80x9d represented by R15 include the above described xe2x80x9clower alkyl groupxe2x80x9d represented by R10. Examples of the xe2x80x9camino group optionally having an optionally substituted hydrocarbon groupxe2x80x9d represented by V include an amino group optionally having one to two of the above described xe2x80x9coptionally substituted hydrocarbon groupxe2x80x9d represented by R1.
The reaction is carried out by reacting the compound (E-I) or (E-II) with the compound (E-III). The reaction is usually carried out in a solvent. Any solvent can be used unless it inhibits this production method.
Examples of the solvent include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, etc., ethers such as dioxane, tetrahydrofuran, diethylether, tert-butylmethylether, diisopropylether, ethyleneglycol-dimethylether, etc., esters such as ethyl formate, ethyl acetate, n-butyl acetate, etc., halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, 1,2-dichloroethane etc., hydrocarbons such as n-hexane, benzene, toluene, etc., amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, etc., ketones such as acetone, methylethylketone, methylisobutylketone, etc., nitriles such as acetonitrile, propionitrile, etc., etc., and additionally dimethylsulfoxide, sulfolane (tetramethylenesulfone), hexamethylphosphorylamide, water, etc., and these can be used singly or as a mixture.
The reaction is usually carried out in the presence of a base. Examples of the base to be employed include a tertiary amine such as trimethylamine, triethylamine, tri(n-propyl)amine, tri(n-butyl)amine, diisopropylethylamine, cyclohexyldimethylamine, pyridine, lutidine, xcex3-collidine, N,N-dimethylaniline, N-methylpiperidine, N-methylpyrrolidine, N-methylmolpholine, etc.; an alkali metal salt such as sodium hydrogen carbonate, potassium carbonate, etc.; an alkali hydroxide such as potassium hydroxide, sodium hydroxide, etc.; an alkoxide such as lithium ethoxide, lithium tert-butoxide, sodium methoxide, sodiumethoxide, carboxyl tert-butoxide, etc.; etc.
In the reaction, about 1 to about 100 moles(preferably about 1 to about 50 moles) of the compound (E-III) is used per 1 mole of the compound (E-I) or (E-II).
The reaction temperature ranges from about xe2x88x9230xc2x0 C. to about 250xc2x0 C., preferably about xe2x88x9210xc2x0 C. to about 200xc2x0 C.
The reaction time varies depending on kind of the compound (E-I), (E-II) or (E-III), kind of the solvent, the reaction temperature, etc. and usually ranges from about 1 minute to about 72 hours, preferably about 15 minutes to about 24 hours.
The starting materials, the compounds (II), (III), (IV), (V) and (VI), used in the above described Methods A to E can be produced by per se known method or a method similar thereto.
In addition, the compounds (D-I), (E-I) and (E-II) can be produced according to the production method of the compound (I) or a method similar thereto.
a) Production method of the compound (II)
i) 
wherein each symbol is as defined above
This production method is carried out by halogenation of the compound (VIII) or a salt thereof (iorganic salt, organic salt, etc.). Examples of the iorganic salt of the compound (VIII) include a salt with alkali metal (e.g. a salt with sodium, a salt with potassium, etc.), a salt with alkaline earth metal (e.g. a salt with calcium, etc.). Examples of the organic salt of the compound (VIII) include a salt with trialkylamine (e.g. a salt with trimethylamine, triethylamine, tert-butyldimethylamine, diisopropylethylamine, etc.), a salt with an aromatic tertiary amine (e.g. N,N-dimethylaniline, pyridine, quinoline, etc.). Examples o a halogenating agent include e.g. phosphorous trichloride, phosphorous tribromide, phosphorous pentachloride, phosphorylchloride, phosphorylbromide, thionylchloride, thionyl-bromide, etc.
The reaction can be carried out by reacting the compound (VIII) with the halogenating agent as a solvent in the presence of no other solvent. The reaction can be carried out in the presence of a solvent other than the halogenating agent. Examples of the solvent include ethers such as dioxane, tetrahydrofuran, diethylether, diisopropyl-ether, dimethoxyethane, etc., halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, etc., aromatic hydrocarbons such as benzene, toluene, chlorobenzene, etc., amides such as N,N-dimethylformamide, N,N-dimethylacetamide, etc., and these can be used singly or as a mixture.
In the reaction, about 1 to about 100 moles (preferably about 1 to about 50 moles) of the halogenating agent is used per 1 mole of the compound (VIII). The reaction temperature ranges from about xe2x88x9230xc2x0 C. to about 250xc2x0 C., preferably about xe2x88x9220xc2x0 C. to about 200xc2x0 C. The reaction time varies depending on kind of the compound (VIII) or the halogenating agent, kind of the solvent, the reaction temperature, etc. and usually ranges from about 1 minute to about 72 hours, preferably about 10 minutes to about 24 hours.
ii) 
wherein L1 is a hydrogen atom or a leaving group, and the other symbols are as defined above.
This production method is carried out by reacting the compound (IX) with chlorine or bromine in the presence of water to produce the compound (II). Examples of the leaving group represented by L1 include xe2x80x94CN, xe2x80x94C(xe2x95x90NH)NH2, etc. The reaction is usually carried out in a solvent and preferable examples of the solvent include that exemplified in the above described Method C. In the reaction, about 1 to about 100 moles, preferably about 1 to about 30 moles of the chlorine or bromine is used per 1 mole of the compound (IX). The reaction temperature ranges from about xe2x88x9250xc2x0 C. to about 180 xc2x0 C., preferably about xe2x88x9230xc2x0 C. to about 120xc2x0 C.
There are many known methods for producing a sulfonyl chloride or a sulfonyl bromide of the compound (II) and the compound (II) can be produced by the above method i) or ii) as well as known methods or a method similar thereto.
b) Production method of the compound (III) 
wherein L2 is a protective group for an amino group, and other symbols are as defined above.
In the above formulas (X) and (XI), examples of the protective group represented by L2 include formyl group, C1-6 alkyl-carbonyl group (e.g. acetyl, ethylcarbonyl, etc.), benzyl group, tert-butyloxycarbonyl group, benzyloxy-carbonyl group, allyloxycarbonyl group, phenylcarbonyl group, C1-6 alkoxy-carbonyl group (e.g. methoxycarbonyl, ethoxycarbonyl, etc.), C7-10 aralkyl-carbonyl group (e.g. benzylcarbonyl, etc.), trityl group, N,N-dimethylaminomethylene group, etc. These protective groups may be substituted with 1 to 3 halogen atoms (e.g. fluorine, chlorine, bromine, etc.), nitro group, etc.
This production method is carried out by reacting the compound (X) with a compound (V) or its reactive derivatives to produce the compound (XI).
The reaction conditions of this production method is the same as described in the above Method B. The compound (III) can be produced by removing the protective group of the compound (XI).
Examples of the method for removing the protective group include per se known methods or a similar method thereto such as a method using acid, base, reduction, ultraviolet light, acetic acid palladium, etc.
C) Production method of the compound (IV) 
wherein L3 is a protective group of an amino group, and the other symbols are as defined above.
In the formulas (XII) and (XIII), the protective group represented by L3 is the same as that represented by L2 in the above method b).
This production method is carried out by reacting the compound (II) with the compound (XII) to produce the compound (XIII). The reaction conditions of this production method are the same as described in the above Method A. The method for removing the protective group of the compound (XIII) is the same as that for the protective group represented by L3 in the above method b).
d) Production method of the compound (V)
i) 
wherein Z1 is an amino group substituted with an optionally substituted hydrocarbon group or an optionally substituted nitrogen-containing heterocyclic group, R5 is a lower alkyl group or an optionally substituted benzyl group, and the other symbols are as defined above.
Examples of the optionally substituted hydrocarbon group, and the substituents f or the optionally substituted hydrocarbon group, the amino group and the optionally substituted nitrogen-containing heterocyclic group represented by Z1 are the same as those of the above Z.
Examples of the lower alkyl group represented by R5 include a C1-6 alkyl group (e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc.), etc., and examples of the substituents for the optionally substituted benzyl group include a lower alkyl group (e.g. C1-6 alkyl group such as methyl, ethyl, propyl, etc.), a lower alkoxy group (e.g. C1-6 alkoxy group such as methoxy, ethoxy, propoxy, etc.), a halogen atom (e.g. fluorine, chlorine, bromine, etc.), etc. One to three of these optional substituent may be substituted at any possible position.
This production method is carried out by reacting the compound (XIV) with the compound (XV) to produce the compound (XVI). The reaction conditions of this production method are the same as described in the above Method C.
ii) 
wherein Z2 is an optionally substituted nitrogen-containing heterocyclic group, L4 is xe2x80x94B(R6)2 (R6 is a hydroxyl group or a lower alkyl group), xe2x80x94ZnT2, xe2x80x94CuT2 (T2 is a halogen atom) or xe2x80x94Sn(R7)3 (R7 is a lower alkyl group), T1 is a halogen atom or xe2x80x94Oxe2x80x94SO2R4, and the other symbols are as defined above.
Examples of the substituents for the optionally substituted nitrogen-containing heterocyclic group represented by Z2 are the same as the above described substituents represented by Z.
Examples of the lower alkyl group represented by R6 and R7 include a C1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, etc. Among others, methyl, ethyl, etc. are preferable. Examples of the halogen atom represented by T1 and T2 include fluorine, chlorine, bromine, iodine, etc.
This production method is usually carried out in a solvent in the presence of an appropriate catalyst and, if necessary, a base. Any solvent can be used unless it inhibits this production method.
Examples of the solvent include alcohols such as methanol, ethanol, propanol, isopropanol, butanol, tert-butanol, etc., ethers such as dioxane, tetrahydrofuran, diethylether, tert-butylmethylether, diisopropylether, ethyleneglycol-dimethylether, etc., esters such as ethyl formate, ethyl acetate, n-butyl acetate, etc., halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, trichloroethylene, 1,2-dichloroethane etc., hydrocarbons such as n-hexane, benzene, toluene, etc., amides such as formamide, N,N-dimethylformamide, N,N-dimethylacetamide, etc., ketones such as acetone, methylethylketone, methylisobutylketone, etc., nitrites such as acetonitrile, propionitrile, etc., etc., and additionally dimethylsulfoxide, sulfolane (tetramethylenesulfone), hexamethylphosphorylamide, water, etc., and these can be used singly or as a mixture.
Preferable examples of the catalyst used in the reaction include a palladium catalyst such as palladium chloride, palladium acetate, chlorobis(triphenylphosphine) palladium, tetrakis(triphenylphosphine) palladium, etc. Examples of the base include potassium hydrogen carbonate, sodium hydrogen carbonate, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, etc.
In the reaction, about 0.5 to about 4 moles (preferably about 0.7 to about 2 moles) of the compound (XVIII) are used per 1 mole of the compound (XVII) and about 0.0001 to about 0.1 mole of the catalyst is used per 1 mole of the compound (XVIII). The reaction temperature ranges from about xe2x88x9290xc2x0 C. to about 150xc2x0 C., preferably about xe2x88x9270xc2x0 C. to about 100xc2x0 C. The reaction time varies depending on the kind of compounds (XVII) and (XVIII), the kind of solvent, the reaction temperature, etc. and usually ranges from about 15 minutes to about 48 hours, preferably about 30 minutes to about 24 hours.
iii) 
wherein Z3 is an optionally substituted nitrogen-containing heterocyclic group, M is an oxygen atom or a sulfur atom, T3 is a halogen atom, R8 is a hydrogen atom or a lower alkyl group, and the other symbols are as defined above.
Examples of the substituents for the optionally substituted nitrogen-containing heterocyclic group represented by Z3 are the same as those for the above Z. Examples of the lower alkyl group represented by R8 include a C1-6 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc.
This production method is carried out by reacting the compound (XX) with the compound (XXI) to produce the compound (XXII). The reaction is usually carried out in a solvent and examples of the solvent are the same as those used in the above method ii).
In the reaction, 1 to 5 moles (preferably 1 to 3 moles) of the compound (XXI) are used per 1 mole of the compound (XX). The reaction temperature ranges from xe2x88x9230xc2x0 C. to 150xc2x0 C., preferably xe2x88x9210xc2x0 C. to 120xc2x0 C. The reaction time varies depending on the kind of compound (XX) or (XXI), the kind of solvent, the reaction temperature, etc. and usually ranges from 5 minutes to 48 hours, preferably 15 minutes to 24 hours.
iv) 
wherein T4 is a halogen atom, and the other symbols are as defined above.
In the above formula, examples of the halogen atom represented by T4 include chlorine, bromine, etc.
This reaction is carried out by reacting the compound (XX) with the compound (XXIII) to produce the compound (XXIV).
The reaction is carried out according to the same method as the above method iii) or a similar method thereto.
v) 
wherein Z4 is an optionally substituted nitrogen-containing heterocyclic group, R9 is a hydrogen atom or a lower alkyl group, and the other symbols are as defined above.
Examples of the substituents for the optionally substituted nitrogen-containing heterocyclic group represented by Z4 are the same as those for the above Z. Examples of the lower alkyl group represented by R9 include a C1-6 alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, etc.
The reaction is usually carried out in a solvent and examples of the solvent are the same as those used in the above method ii).
In the reaction, 0.8 to 5 moles (preferably 0.9 to 3 moles) of the compound (XXVI) are used per 1 mole of the compound (XXV). The reaction temperature and the reaction are the same conditions as described in the above described method iv).
The compounds (XVI), (XIX), (XXII), (XXIV) and (XXVII) produced according to the above-described methods can be transformed into a free acid form, if desired. For example, when R5is a lower alkyl group, hydrolysis with acid or alkali is employed. Preferable examples of the acid include hydrochloric acid, sulfuric acid, hydrobromic acid, etc. Preferable examples of the alkali include lithium hydroxide, potassium hydroxide, sodium hydroxide, calcium hydride, etc. When R5 is an optionally substituted benzyl group, in addition to the above hydrolysis with acid or alkali, catalytic reduction (catalytic hydrogenation) can be employed to produce a free acid. In the catalytic reduction, catalysts are employed. Examples of the catalyst include platinum catalyst such as platinum oxide, platinum black, platinum carbon, etc., palladium catalyst such as palladium chloride, palladium black, palladium carbon, etc., rhodium catalyst such as rhodium carbon, rhodium almina, etc., Raney nickel, etc. The reduction reaction can be carried out under high pressure, if necessary, and said pressure ranges from about 1 to about 50 times atmospheric pressure, preferably about 1 to about 20 times atmospheric pressure. The reaction is usually carried out in a solvent and examples of the solvent are the same as that described in the above method ii). The reaction temperature ranges from about xe2x88x9210xc2x0 C. to about 150xc2x0 C., preferably about xe2x88x925xc2x0 C. to about 120xc2x0 C. The reaction time varies depending on kind of the compound, the solvent and the catalyst, and usually ranges from about 15 minutes to about 72 hours, preferably about 30 minutes to about 24 hours.
When a free form of the compound is obtained according to the above described reaction of the present invention, it can be transformed into a salt thereof according to per se methods. When a salt of the compound is obtained according to the above described reaction of the present invention, it can be transformed into a free form thereof according to per se methods.
The compound (I) of this invention can be isolated from the reaction mixture by a conventional methods separation and purification means such as extraction, concentration, neutralization, filtration, recrystallization, column chromatography and thin-layer chromatography, etc.
Salts of the compound (I) can be obtained by per se known methods, e.g. by adding an inorganic acid or an organic acid to the compound (I).
When stereoisomers are present in the compounds (I), individual isomers or a mixture thereof are included in the scope of the present invention. And, it is also possible to produce these isomers individually.
The compounds (I), (I-1) and (I-2) may be hydrated or solvated.
The compounds (I) of the present invention or a salt thereof are low in toxicity, inhibit FXa and have anti-coagulant activity, therefore, they are useful for the prevention or treatment of the following diseases of animals, especially mammals (e.g. human, monkey, cat, pig, horse, cow, mouse, rat, guinea pig, dog, rabbit, etc.). Among others, they are preferably used for the prevention or treatment of cerebral infarction (especially due to atrial fibrillation or auricular fibrillation), deep vein thrombosis, etc.
brain:
cerebral infarction due to atrial fibrillation or auricular fibrillation, acute ischemic cerebral apoplexy, acute phase cerebral thrombosis , cerebral vasospasm after subarachnoid hemorrhage, Alzheimer""s disease, transient ischemic attack (TIA), mixed dementia, cerebrovascular dementia, multiple sclerosis dementia,
heart:
acute cardiac infarction, sequela of cardiac infarction, unstable angina, angina pectoris, reobturation or restenosis after, stent-indwelling, PTCA (percutaneous transluminol coronary angioplasty), atherectomy, coronary intervention,
periphery:
deep vein thrombosis, pulmonary embolism, peripheral arterial obstruction, adult respiratory distress syndrome (ARDS), chronic renal disease (e.g. diabetic nephropathy, chronicglomerulonephrits, IgA nephropathy, etc.), diabetic cardiovascular disorder, diabetic pain, diabetic nerve disturbance, thrombosis due to hip and knee replacement surgeries,
others:
thrombocytopenia due to dialysis, thrombocytopenia due to operation, arteriosclerosis, cancer metastasis, systemic inflammation reaction syndrome (SIRS) or disseminated intravascular coagulation (DIC) in cases of pancreatitis, sepsis or cancer, rejection after transplantation, protecting organs or ameliorating function of organs after transplantation, various organ failure (e.g. pulmonary failure, hepatic insufficiency, renal insufficiency, heart failure, etc.) due to shock or DIC.
The compound (I) of the present invention or a salt thereof, alone or in combination with a pharmaceutically acceptable carrier, can be administered orally or non-orally.
Examples of pharmaceutical composition for oral administration of the compound (I) or a salt thereof of the present invention include tablets (including sugar-coated tablet, film coating tablet), pills, granules, powders, capsules (including soft capsules), syrups, emulsions, suspensions, etc. Examples of pharmaceutical composition for oral administration of the compound (I) or a salt thereof of the present invention include injections, inhalations, drops, suppositories, etc.
The content of the compound (I) or a salt thereof in the pharmaceutical composition of this invention varies depending on a kind of formulations and is usually about 2 to about 85 weight %, preferably about 5 to about 70 weight % based on the total weight of the composition.
Examples of the method for preparing the pharmaceutical compositions containing the compound (I) or a salt thereof include conventional methods generally used in this field. In addition, when the above pharmaceutical compositions are prepared, if desired, an appropriate amount of an additive which is generally used in this field such as an excipient, a binder, an disintegrating agent, a lubricant, a sweetener, a surfactant, a suspending agent, an emulsifier, etc. can be added to the compositions.
For example, a tablet of the compound (I) or a salt thereof may contain an excipient, a binder, an disintegrating agent, a lubricant, etc.; a pill and a granulate may contain an excipient, a binder, an disintegrating agent, etc.; a powder and a capsule may contain an excipient, etc.; a syrup may contain a sweetener, etc.; and an emulsion or a suspension may contain a surfactant, a suspending agent, an emulsifier, etc.
Examples of the excipient include lactose, sucrose, glucose. starch, fine crystalline cellulose, powdered glycyrrhiza, mannitol, sodium hydrogen carbonate, calcium phosphorate, calcium sulfate, etc.
Examples of the binder include 5 to 10 weight % of starch solution, 10 to 20 weight % of gum arabic or gelatin solution, 1 to 5 weight % of traganth solution, carboxy-methylcellulose solution, sodium alginate solution, glycerin, etc.
Examples of the disintegrating agent include starch, calcium carbonate ,etc.
Examples of the lubricant include magnesium stearate, stearic acid, calcium stearate, purified talc, etc.
Examples of the sweetener include glucose, fructose, invert sugar, sorbitol, xylitol, glycerin, simple syrup, etc.
Examples of the surfactant include sodium lauryl sulfate, polysorbate 80, sorbitan mono fatty acid ester, stearic acid, polyoxyl 40, etc.
Examples of the suspending agent include gum arabic, sodium alginate, sodium carboxymethylsellulose, methyl-cellulose, bentonite, etc.
Examples of the emulsifier include gum arabic, traganth, gelatin, polysorbate 80, etc.
In additition, when the above described compositions are prepared, if desired, an appropriate amount of a colorant, a preservative, an aromatic, a flavoring, a stabilizer, a viscous liquid, etc. which is generally used in this field can be added to the compositions.
The compound (I) or a salt thereof is low in toxicity and stable, therefore, it can be used safely. While the dosage of the compound (I) can vary with condition or body weight of patients, kind of the compound and administration routes, etc., when administered orally to a patient of e.g. thrombosis, a dose of about 1 to 1000 mg, preferably about 3 to 300 mg, more preferably about 1 to 20 mg of the active ingredient [compound (I)], per day for an adult (body weight: about 60 kg), divided into one to three times, is appropriate.
The pharmaceutical composition of the present invention can be used in combination with thrombolytic drug (e.g. tPA, heparin, urokinase, etc.), drug for treating Alzheimer""s disease (e.g. Avan, Calan, etc.), drug for treating cholesterol (e.g. HMG-CoA reductase inhibitor such as Simvastatin, Pravastatin, etc., etc.), TG (triglyceride) decreasing drug (antihyperlipoproteinemic agent) (e.g. Clofibrate, etc.), AII antagonist (e.g. Blopress, etc.), anti-thrombocyte drug (e.g. aspirin, etc.), Ca antagonist (e.g. Calslot, Amlodipine, etc.) etc., or the active ingredient of these drugs can be added to the pharmaceutical composition of the present invention.